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Antimicrobial Resistance during the COVID-19 Outbreak

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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 October 2023) | Viewed by 22643

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Dr. Mirela Loredana Grigoraş

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Department of Anatomy and Embryology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Timisoara, Romania
Interests: COVID-19; clinical
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Prof. Dr. Cristian Oancea

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Pulmonology Department, University of Medicine and Pharmacy Victor Babes, Timisoara, Romania
Interests: respiratory system; cognition; cardiovascular health
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Dr. Cosmin Citu

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Department of Obstetrics and Gynecology, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania
Interests: obstetrics; maternal–fetal medicine; infectious disease; prediction
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Special Issue Information

Dear Colleagues,

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent pandemic has placed an immense strain on healthcare systems worldwide. The challenges posed by the diagnosis and management of coronavirus disease 2019 (COVID-19) together with concerns regarding associated bacterial and fungal infection have promoted the extensive use of antimicrobials in acute care. In contrast, in the community, we have observed a reduction of antimicrobial use. The impact that the COVID-19 pandemic will have on antimicrobial resistance in the long term remains unknown.

We are pleased to invite you to contribute to this Special Issue of Antibiotics. The aim of this Special Issue is to provide insights into the impact of COVID-19 on antimicrobial use and antimicrobial resistance. We also aim to highlight and discuss specific interventions that have been developed to address inappropriate antimicrobial use and antimicrobial resistance during the pandemic.

Dr. Mirela Grigoraș
Prof. Dr. Cristian Oancea
Dr. Cosmin Citu
Guest Editors

Manuscript Submission Information

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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 stewardship
antimicrobial resistance
COVID-19
SARS-CoV-2
diagnostics
interventions
co-infection
healthcare-associated infection

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Published Papers (10 papers)

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18 pages, 891 KiB

Open AccessArticle

A COVID-19 Silver Lining—Decline in Antibiotic Resistance in Ischemic Leg Ulcers during the Pandemic: A 6-Year Retrospective Study from a Regional Tertiary Hospital (2017–2022)

by Amaraporn Rerkasem, Pak Thaichana, Nuttida Bunsermvicha, Rawee Nopparatkailas, Supapong Arwon, Saranat Orrapin, Termpong Reanpang, Poon Apichartpiyakul, Saritphat Orrapin, Boonying Siribumrungwong, Nongkran Lumjuan, Kittipan Rerkasem and José G. B. Derraik

Antibiotics 2024, 13(1), 35; https://doi.org/10.3390/antibiotics13010035 - 29 Dec 2023

Viewed by 1749

Abstract

Antibiotic resistance (AR) associated with chronic limb-threatening ischemia (CLTI) poses additional challenges for the management of ischemic leg ulcers, increasing the likelihood of severe outcomes. This study assessed AR prevalence in bacteria isolated from CLTI-associated leg ulcers before (1 January 2017–10 March 2020; n = 69) and during (11 March 2020–31 December 2022; n = 59) the COVID-19 pandemic from patients admitted with positive wound cultures to a regional hospital in Chiang Mai (Thailand). There was a marked reduction in AR rates from 78% pre-pandemic to 42% during the pandemic (p < 0.0001), with rates of polymicrobial infections 22 percentage points lower (from 61% to 39%, respectively; p = 0.014). There were reduced AR rates to amoxicillin/clavulanate (from 42% to 4%; p < 0.0001) and ampicillin (from 16% to 2%; p = 0.017), as well as multidrug resistance (19% to 8%; p = 0.026). Factors associated with increased AR odds were polymicrobial infections (adjusted odds ratio (aOR) 5.6 (95% CI 2.1, 15.0); p = 0.001), gram-negative bacteria (aOR 7.0 (95% CI 2.4, 20.5); p < 0.001), and prior use of antibiotics (aOR 11.9 (95% CI 1.1, 128.2); p = 0.041). Improvements in infection control measures and hygiene practices in the community during the pandemic were likely key factors contributing to lower AR rates. Thus, strategic public health interventions, including community education on hygiene and the informed use of antibiotics, may be crucial in mitigating the challenges posed by AR in CLTI. Further, advocating for more judicious use of empirical antibiotics in clinical settings can balance effective treatment against AR development, thereby improving patient outcomes. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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15 pages, 850 KiB

Open AccessArticle

Molecular Typing and Resistance Profile of Acinetobacter baumannii Isolates during the COVID-19 Pandemic: Findings from the “EPIRADIOCLINF” Project

by Antonella Agodi, Arturo Montineri, Rosa Manuele, Paola Noto, Giuseppe Carpinteri, Giacomo Castiglione, Patrizia Grassi, Antonio Lazzara, Anna Rita Mattaliano, Giuseppa Granvillano, Claudia La Mastra, Maria Clara La Rosa, Andrea Maugeri and Martina Barchitta

Antibiotics 2023, 12(10), 1551; https://doi.org/10.3390/antibiotics12101551 - 19 Oct 2023

Viewed by 1775

Abstract

Due to the COVID-19 pandemic, there has been a shift in focus towards controlling the spread of SARS-CoV-2, which has resulted in the neglect of traditional programs aimed at preventing healthcare-associated infections and combating antimicrobial resistance. The present work aims to characterize the colonization or infection with Acinetobacter baumannii of COVID-19 patients and to identify any clonality between different isolates. Specifically, data and resistance profiles of A. baumannii isolates were prospectively collected from patients recruited by the EPIRADIOCLINF project. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used for molecular typing. Overall, we analyzed 64 isolates of A. baumannii from 48 COVID-19 patients. According to our analysis, we have identified the spread of a clonally related isolate, referred to as B. The PFGE pattern B includes four subtypes: B1 (consisting of 37 strains), B2 (11), B3 (5), and B4 (2). Furthermore, in the isolates that were examined using MLST, the most observed sequence type was ST/281. In terms of resistance profiles, 59 out of the total isolates (92.2%) were found to be resistant to gentamicin, carbapenems, ciprofloxacin, and tobramycin. The isolation and identification of A. baumannii from COVID-19 patients, along with the high levels of transmission observed within the hospital setting, highlight the urgent need for the implementation of effective prevention and containment strategies. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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12 pages, 2147 KiB

Open AccessArticle

Microbial Landscape and Antibiotic-Susceptibility Profiles of Microorganisms in Patients with Bacterial Pneumonia: A Comparative Cross-Sectional Study of COVID-19 and Non-COVID-19 Cases in Aktobe, Kazakhstan

by Nurgul Ablakimova, Aigul Z. Mussina, Gaziza A. Smagulova, Svetlana Rachina, Meirambek S. Kurmangazin, Aigerim Balapasheva, Dinara Karimoldayeva, Afshin Zare, Mahdi Mahdipour and Farhad Rahmanifar

Antibiotics 2023, 12(8), 1297; https://doi.org/10.3390/antibiotics12081297 - 8 Aug 2023

Cited by 3 | Viewed by 1839

Abstract

This cross-sectional study investigated the microbial landscape and antibiotic-resistance patterns in patients with bacterial pneumonia, with a focus on the impact of COVID-19. Sputum samples from individuals with bacterial pneumonia, including coronavirus disease 2019-positive polymerase chain reaction (COVID-19-PCR+), COVID-19-PCR− and non-COVID-19 patients, were analyzed. Surprisingly, the classic etiological factor of bacterial pneumonia, Streptococcus pneumoniae, was rarely isolated from the sputum samples. Furthermore, the frequency of multidrug-resistant pathogens was found to be higher in non-COVID-19 patients, highlighting the potential impact of the pandemic on antimicrobial resistance. Strains obtained from COVID-19-PCR+ patients exhibited significant resistance to commonly used antibiotics, including fluoroquinolones and cephalosporins. Notably, the ESKAPE pathogens, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Enterobacter aerogenes, were identified among the isolated microorganisms. Our findings underscore the urgent need for infection control measures and responsible antibiotic use in healthcare settings, as well as the importance of enhancing pneumonia diagnostics and implementing standardized laboratory protocols. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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11 pages, 1530 KiB

Open AccessArticle

Impact of the COVID-19 Pandemic on Epidemiology of Antibiotic Resistance in an Intensive Care Unit (ICU): The Experience of a North-West Italian Center

by Andrea Parisini, Silvia Boni, Elisabetta Blasi Vacca, Nicoletta Bobbio, Filippo Del Puente, Marcello Feasi, Roberta Prinapori, Marco Lattuada, Marina Sartini, Maria Luisa Cristina, David Usiglio and Emanuele Pontali

Antibiotics 2023, 12(8), 1278; https://doi.org/10.3390/antibiotics12081278 - 3 Aug 2023

Cited by 8 | Viewed by 1867

Abstract

The SARS-CoV-2 pandemic caused an increase in intensive care unit (ICU) hospitalizations with a rise in morbidity and mortality; nevertheless, there is still little evidence on the impact of the pandemic on antibiotic resistance in ICUs. This is a retrospective, monocentric epidemiological study. The aim of the study was to describe and analyze the impact of the SARS-CoV-2 pandemic on ICU bacterial resistance patterns. All bacteria isolated from all patients admitted to the E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. A total of 1021 microorganisms were identified, of which 221 (12.47%) had a resistance pattern (resistant organisms; ROs). In this time, there were 1679 patients with a total of 12,030 hospitalization days. The majority of microorganisms were Gram-negative (79.66% in 2018, 77.29% in 2019, 61.83% in 2020, 62.56% in 2021, and 60.75% in 2022), but an increase in Gram-positive microorganisms was observed (20.34 to 39.25% between 2018 and 2022). The prevalence of AR was 19.44% in 2018, 11.54% in 2019, 38.04% in 2020, 34.15% in 2021, and 39.29% in 2022 for Gram-positive microorganisms and 19.86% in 2018, 13.56% in 2019, 18.12% in 2020, 12.41% in 2021, and 12.31% in 2012 for Gram-negative microorganisms. The incidence of ROs showed a COVID-19-related increase in 2020–2021, followed by a lowering trend since 2021, and a new increase in 2022. Possible explanations are antibiotic overtreatment and a decrease in containment measures. An interesting finding was the cumulative lowering trend of carbapenem-resistant K. pneumoniae and P. aeruginosa, probably due to different patient features. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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11 pages, 550 KiB

Open AccessFeature PaperArticle

Real-World Data Regarding Dalbavancin Use before and during the COVID-19 Pandemic—A Single-Center Retrospective Study

by Petros Ioannou, Nora Wolff, Anna Mathioudaki, Christos Spanias, Nikolaos Spernovasilis and Diamantis P. Kofteridis

Antibiotics 2023, 12(7), 1205; https://doi.org/10.3390/antibiotics12071205 - 19 Jul 2023

Cited by 3 | Viewed by 2186

Abstract

Dalbavancin is a semisynthetic lipoglycopeptide, which possesses great potential for bactericidal activity similar to antimicrobials with the same mechanism of action, such as vancomycin and teicoplanin. Due to its very prolonged half-life, it can be used in a single or two-dose regimen to treat infections by Gram-positive microorganisms, even resistant ones, such as methicillin-resistant Staphylococcus aureus (MRSA). Currently, it is approved only for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). The aim of this study was to investigate the clinical and microbiological characteristics of patients to whom dalbavancin was administered at the University Hospital of Heraklion and evaluate its use in regard to the COVID-19 pandemic. In total, 146 patients were included in this retrospective cohort study evaluating the use of dalbavancin from the first time it was used in 2017 until the end of 2022. The median age was 68 years (range: 21–96 years), and 86 (59%) patients were male. The most common indications for dalbavancin use were osteoarticular infections in 43%, followed by ABSSSIs in 37%, and cardiovascular infections in 10%. Dalbavancin was used empirically in one out of three patients, most commonly with the indication of ABSSSIs, and most commonly in the post-COVID-19 era. The most frequently isolated pathogens were coagulase-negative staphylococci in 70%, S. aureus in 27%, Enterococcus spp. in 22%, and Streptococcus spp. in 8%, while one out of three infections were polymicrobial. In 12% of patients, the infection was not cured, but no patients died. For patients with ABSSSIs, endocarditis and vascular infections, and bacteremia, the cure rates were more than 90%, and in osteoarticular infections, the cure rate was 76%. Thus, dalbavancin has great potential for use in complicated and invasive infections that may require prolonged intravenous antimicrobial treatment. However, further studies are required to formally investigate its role in such infections. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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13 pages, 1576 KiB

Open AccessArticle

Prevalence and Antibiotic Resistance Pattern of Streptococcus, Staphylococcus, Neisseria meningitidis and Enterobacteriaceae in Two Reference Hospitals of Yaoundé: An Overview before and during COVID-19 Pandemic Era

by Cecile Ingrid Djuikoue, Willy Yamdeu Djonkouh, Cavin Epie Bekolo, Rodrigue Kamga Wouambo, Raspail Carrel Founou, Paule Dana Djouela Djoulako, Gilder Tonfak Temgoua, Benjamin D. Thumamo Pokam, Nicolas Antoine-Moussiaux and Teke R. Apalata

Antibiotics 2023, 12(5), 929; https://doi.org/10.3390/antibiotics12050929 - 18 May 2023

Cited by 2 | Viewed by 2797

Abstract

The COVID-19 pandemic led to tremendously use of antimicrobial due to the lack of proper treatment strategies, raising concerns about emergence of antimicrobial resistance (AMR). This study aimed at determining the prevalence and antibiotic resistance pattern of selected bacteria isolates in 02 referral health facilities in Yaoundé before and during the COVID-19 pandemic era. We conducted a retrospective study over a period of 03 years (from 1 January 2019 to 31 December 2021) in the bacteriology units of the Central and General Hospitals of Yaoundé, Cameroon. Data on bacteria genera (Streptococcus, Staphylococcus, Neisseria meningitidis and Enterobacteriaceae) as well as their corresponding specifics antibiotics: Cefixime, azythromycin and erythromycin were obtained from laboratory records. The global resistance rate of bacteria as well as their correlation with antibiotics according to COVID-19 pandemic era was determined and compared. For p < 0.05, the difference was statistically significant. In all, 426 bacterial strains were included. It appeared that the highest number of bacteria isolates and lowest rate of bacterial resistance were recorded during the pre-COVID-19 period in 2019 (160 isolates vs. 58.8% resistance rate). Conversely, lower bacteria strains but greater resistance burden were recorded during the pandemic era (2020 and 2021) with the lowest bacteria amount and peak of bacteria resistance registered in 2020, the year of COVID-19 onset (120 isolates vs. 70% resistance in 2020 and 146 isolates vs. 58.9% resistance in 2021). In contrast to almost all others groups of bacteria where the resistance burden was quite constant or decreasing over years, the Enterobacteriaceae exhibited greater resistance rate during the pandemic period [60% (48/80) in 2019 to 86.9% (60/69) in 2020 and 64.5% (61/95) in 2021)]. Concerning antibiotics, unlike erythromycin, azythromycin related resitance increased during the pandemic period and the resistance to Cefixim tends to decrease the year of the pandemic onset (2020) and re-increase one year therafter. A significant association was found between resistant Enterobacteriaceae strains and cefixime (R = 0.7; p = 0.0001) and also, between resistant Staphylococcus strains and erythromycin (R = 0.8; p = 0.0001). These retrospective data showed a herogeneous MDR bacteria rate and antibiotic resistance pattern over time before and during the COVID-19 pandemic era suggesting that antimicrobial resistance needs to be more closely monitored. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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14 pages, 3068 KiB

Open AccessArticle

On the Potential of Relational Databases for the Detection of Clusters of Infection and Antibiotic Resistance Patterns

by Michela Gelfusa, Andrea Murari, Gian Marco Ludovici, Cristiano Franchi, Claudio Gelfusa, Andrea Malizia, Pasqualino Gaudio, Giovanni Farinelli, Giacinto Panella, Carla Gargiulo and Katia Casinelli

Antibiotics 2023, 12(4), 784; https://doi.org/10.3390/antibiotics12040784 - 19 Apr 2023

Cited by 1 | Viewed by 1504

Abstract

In recent years, several bacterial strains have acquired significant antibiotic resistance and can, therefore, become difficult to contain. To counteract such trends, relational databases can be a powerful tool for supporting the decision-making process. The case of Klebsiella pneumoniae diffusion in a central region of Italy was analyzed as a case study. A specific relational database is shown to provide very detailed and timely information about the spatial–temporal diffusion of the contagion, together with a clear assessment of the multidrug resistance of the strains. The analysis is particularized for both internal and external patients. Tools such as the one proposed can, therefore, be considered important elements in the identification of infection hotspots, a key ingredient of any strategy to reduce the diffusion of an infectious disease at the community level and in hospitals. These types of tools are also very valuable in the decision-making process related to antibiotic prescription and to the management of stockpiles. The application of this processing technology to viral diseases such as COVID-19 is under investigation. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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10 pages, 508 KiB

Open AccessArticle

Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis

by Milo Gatti, Giacomo Fornaro, Zeno Pasquini, Andrea Zanoni, Michele Bartoletti, Pierluigi Viale and Federico Pea

Antibiotics 2023, 12(4), 764; https://doi.org/10.3390/antibiotics12040764 - 16 Apr 2023

Cited by 4 | Viewed by 1854

Abstract

(1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA between January 2021 and December 2022 were included. The concentration/dose ratio (C/D) was used as a surrogate marker of voriconazole total clearance. A receiving operating characteristic (ROC) curve analysis was performed by using C-reactive protein (CRP) or procalcitonin (PCT) values as the test variable and voriconazole C/D ratio > 0.375 (equivalent to a trough concentration [C_min] value of 3 mg/L normalized to the maintenance dose of 8 mg/kg/day) as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated; (3) Results: Overall, 50 patients were included. The median average voriconazole C_min was 2.47 (1.75–3.33) mg/L. The median (IQR) voriconazole concentration/dose ratio (C/D) was 0.29 (0.14–0.46). A CRP value > 11.46 mg/dL was associated with the achievement of voriconazole C_min > 3 mg/L, with an AUC of 0.667 (95% CI 0.593–0.735; p < 0.001). A PCT value > 0.3 ng/mL was associated with the attainment of voriconazole C_min > 3 mg/L (AUC 0.651; 95% CI 0.572–0.725; p = 0.0015). (4) Conclusions: Our findings suggest that in critically ill patients with CAPA, CRP and PCT values above the identified thresholds may cause the downregulation of voriconazole metabolism and favor voriconazole overexposure, leading to potentially toxic concentrations. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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18 pages, 5244 KiB

Open AccessArticle

Procalcitonin Values Fail to Track the Presence of Secondary Bacterial Infections in COVID-19 ICU Patients

by Elsa Harte, Sharuha Kumarasamysarma, Benjamin Phillips, Olivia Mackay, Zohra Rashid, Natalya Malikova, Abdullah Mukit, Saraswathi Ramachandran, Anna Biju, Kate Brown, Rosie Watts, Charlie Hodges, William Tuckwell, Nick Wetherall, Henry Breen, Shannon Price and Tamas Szakmany

Antibiotics 2023, 12(4), 709; https://doi.org/10.3390/antibiotics12040709 - 5 Apr 2023

Cited by 5 | Viewed by 3332

Abstract

The development of secondary bacterial infections in COVID-19 patients has been associated with increased mortality and worse clinical outcomes. Consequently, many patients have received empirical antibiotic therapies with the potential to further exacerbate an ongoing antimicrobial resistance crisis. The pandemic has seen a rise in the use of procalcitonin testing to guide antimicrobial prescribing, although its value remains elusive. This single-centre retrospective study sought to analyse the efficacy of procalcitonin in identifying secondary infections in COVID-19 patients and evaluate the proportion of patients prescribed antibiotics to those with confirmed secondary infection. Inclusion criteria comprised patients admitted to the Grange University Hospital intensive care unit with SARS-CoV-2 infection throughout the second and third waves of the pandemic. Data collected included daily inflammatory biomarkers, antimicrobial prescriptions, and microbiologically proven secondary infections. There was no statistically significant difference between PCT, WBC, or CRP values in those with an infection versus those without. A total of 57.02% of patients had a confirmed secondary infection, with 80.2% prescribed antibiotics in Wave 2, compared to 44.07% with confirmed infection and 52.1% prescribed antibiotics in Wave 3. In conclusion, procalcitonin values failed to indicate the emergence of critical care-acquired infection in COVID-19 patients. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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Review

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19 pages, 1613 KiB

Open AccessReview

Antimicrobial Resistance: Is There a ‘Light’ at the End of the Tunnel?

by Leon G. Leanse, Sanjay Marasini, Carolina dos Anjos and Tianhong Dai

Antibiotics 2023, 12(9), 1437; https://doi.org/10.3390/antibiotics12091437 - 12 Sep 2023

Cited by 9 | Viewed by 2323

Abstract

In recent years, with the increases in microorganisms that express a multitude of antimicrobial resistance (AMR) mechanisms, the threat of antimicrobial resistance in the global population has reached critical levels. The introduction of the COVID-19 pandemic has further contributed to the influx of infections caused by multidrug-resistant organisms (MDROs), which has placed significant pressure on healthcare systems. For over a century, the potential for light-based approaches targeted at combatting both cancer and infectious diseases has been proposed. They offer effective killing of microbial pathogens, regardless of AMR status, and have not typically been associated with high propensities of resistance development. To that end, the goal of this review is to describe the different mechanisms that drive AMR, including intrinsic, phenotypic, and acquired resistance mechanisms. Additionally, the different light-based approaches, including antimicrobial photodynamic therapy (aPDT), antimicrobial blue light (aBL), and ultraviolet (UV) light, will be discussed as potential alternatives or adjunct therapies with conventional antimicrobials. Lastly, we will evaluate the feasibility and requirements associated with integration of light-based approaches into the clinical pipeline. Full article

(This article belongs to the Special Issue Antimicrobial Resistance during the COVID-19 Outbreak)

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