Antimicrobial Therapy in Intensive Care Unit

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 (30 June 2022) | Viewed by 60320

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Special Issue Editors

2nd Department of Intensive Care, School of Medicine, National and Kapodistrian University of Athens, 'Attikon' Hospital, Athens, Greece
Interests: infection control in the critically ill; multi-resistant bacteria; rapid detection; antibiotic therapy
Medical School, National and Kapodistrian University of Athens, ICU Evangelismos Hospital, Athens, Greece
Interests: ICU-acquired infections; multidrug resistant bacteria; sepsis; septic shock
Faculté de Médecine, Université de Paris, Paris, France
Interests: antibiotics; antimicrobial resistance; impact of antibiotics on the intestinal flora microbiota

Special Issue Information

Dear Colleagues,

Antimicrobial therapy in the intensive care unit (ICU) is one of the greatest challenges of contemporary medicine. The introduction of new antibiotics and antifungals in the arsenal of physicians peaked in the 1990s and 2000s but was then followed by drying up of the antibiotic pipeline in parallel with the emergence of multi- and pan-resistant bacteria. Newer antimicrobials introduced after 2010 include combinations of already existing substances, rather than new categories, with very few exceptions, and are therefore not sufficient to cover the unmet needs of critically ill patients. Furthermore, the extended use of antifungals has contributed to the shift of the Candida spectrum toward non-albicans species. The arising therapeutic problems are more prominent in the ICU setting, where patients are more vulnerable. Newer pandemics such as COVID-19 and the resulting overuse of antibiotics are adding to the existing burden. For all the abovementioned reasons, this Special Issue seeks manuscript submissions that further our understanding on antimicrobial use in intensive care units.

Authors are invited to submit manuscripts of original preclinical and clinical research as well as narrative and systematic reviews/meta-analysis within their area of interest including (but not limited) to the topics highlighted below:

- Antibiotic optimization, including PK/PD;

- Novel antibiotics, antifungals, and antivirals, branded or emerging;

- Alternative to antibiotics approaches to prevent or tackle infections, such as antibodies, bacteriophages, vaccines, immunotherapeutics;

- De-escalation;

- Antibiotic stewardship, including strategies to combat antibiotic overuse and combat resistance;

- Antibiotic access, antibiotic innovation;

- Microbiota.

Dr. Elizabeth Paramythiotou
Prof. Dr. Christina Routsi
Dr. Antoine Andremont
Guest Editors

Manuscript Submission Information

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

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

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

Keywords

  • antimicrobial therapy
  • antibiotic optimization
  • novel antimicrobials
  • alternative to antibiotics approaches
  • antifungals
  • antiviral treatment
  • antibiotic stewardship
  • antibiotic access
  • antibiotic innovation
  • intensive care unit

Published Papers (16 papers)

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Editorial

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4 pages, 179 KiB  
Editorial
Editorial for Special Issue “Antimicrobial Therapy in Intensive Care Unit”
by Elizabeth Paramythiotou and Christina Routsi
Antibiotics 2023, 12(2), 278; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics12020278 - 31 Jan 2023
Viewed by 923
Abstract
Life-threatening infections, either as the initial reason for an admission to the intensive care unit (ICU) or acquired in the ICU, are especially common among critically ill patients [...] Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)

Research

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19 pages, 837 KiB  
Article
Plethora of Antibiotics Usage and Evaluation of Carbapenem Prescribing Pattern in Intensive Care Units: A Single-Center Experience of Malaysian Academic Hospital
by Chee Lan Lau, Petrick Periyasamy, Muhd Nordin Saud, Sarah Anne Robert, Lay Yen Gan, Suet Yin Chin, Kiew Bing Pau, Shue Hong Kong, Farah Waheeda Tajurudin, Mei Kuen Yin, Sheah Lin Ghan, Nur Jannah Azman, Xin Yun Chua, Poy Kei Lye, Stephanie Wai Yee Tan, Dexter Van Dort, Ramliza Ramli, Toh Leong Tan, Aliza Mohamad Yusof, Saw Kian Cheah, Wan Rahiza Wan Mat and Isa Naina-Mohamedadd Show full author list remove Hide full author list
Antibiotics 2022, 11(9), 1172; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11091172 - 30 Aug 2022
Cited by 3 | Viewed by 1924
Abstract
Excessive antibiotic consumption is still common among critically ill patients admitted to intensive care units (ICU), especially during the coronavirus disease 2019 (COVID-19) period. Moreover, information regarding antimicrobial consumption among ICUs in South-East Asia remains scarce and limited. This study aims to determine [...] Read more.
Excessive antibiotic consumption is still common among critically ill patients admitted to intensive care units (ICU), especially during the coronavirus disease 2019 (COVID-19) period. Moreover, information regarding antimicrobial consumption among ICUs in South-East Asia remains scarce and limited. This study aims to determine antibiotics utilization in ICUs by measuring antibiotics consumption over the past six years (2016–2021) and specifically evaluating carbapenems prescribed in a COVID-19 ICU and a general intensive care unit (GICU) during the second year of the COVID-19 pandemic. (2) Methods: This is a retrospective cross-sectional observational analysis of antibiotics consumption and carbapenems prescriptions. Antibiotic utilization data were estimated using the WHO Defined Daily Doses (DDD). Carbapenems prescription information was extracted from the audits conducted by ward pharmacists. Patients who were prescribed carbapenems during their admission to COVID-19 ICU and GICU were included. Patients who passed away before being reviewed by the pharmacists were excluded. (3) Results: In general, antibiotics consumption increased markedly in the year 2021 when compared to previous years. Majority of carbapenems were prescribed empirically (86.8%). Comparing COVID-19 ICU and GICU, the reasons for empirical carbapenems therapy in COVID-19 ICU was predominantly for therapy escalation (64.7% COVID-19 ICU vs. 34% GICU, p < 0.001), whereas empirical prescription in GICU was for coverage of extended-spectrum beta-lactamases (ESBL) gram-negative bacteria (GNB) (45.3% GICU vs. 22.4% COVID-19 ICU, p = 0.005). Despite microbiological evidence, the empirical carbapenems were continued for a median (interquartile range (IQR)) of seven (5–8) days. This implies the need for a rapid diagnostic assay on direct specimens, together with comprehensive antimicrobial stewardship (AMS) discourse with intensivists to address this issue. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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9 pages, 230 KiB  
Article
Incidence and Risk Factors for Blood Stream Infection in Mechanically Ventilated COVID-19 Patients
by Konstantinos Mantzarlis, Konstantina Deskata, Dimitra Papaspyrou, Vassiliki Leontopoulou, Vassiliki Tsolaki, Epaminondas Zakynthinos and Demosthenes Makris
Antibiotics 2022, 11(8), 1053; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11081053 - 03 Aug 2022
Cited by 8 | Viewed by 1473
Abstract
It is widely known that blood stream infections (BSIs) in critically ill patients may affect mortality, length of stay, or the duration of mechanical ventilation. There is scarce data regarding blood stream infections in mechanically ventilated COVID-19 patients. Preliminary studies report that the [...] Read more.
It is widely known that blood stream infections (BSIs) in critically ill patients may affect mortality, length of stay, or the duration of mechanical ventilation. There is scarce data regarding blood stream infections in mechanically ventilated COVID-19 patients. Preliminary studies report that the number of secondary infections in COVID-9 patients may be higher. This retrospective analysis was conducted to determine the incidence of BSI. Furthermore, risk factors, mortality, and other outcomes were analyzed. The setting was an Intensive Care Unit (ICU) at a University Hospital. Patients suffering from SARS-CoV-2 infection and requiring mechanical ventilation (MV) for >48 h were eligible. The characteristics of patients who presented BSI were compared with those of patients who did not present BSI. Eighty-four patients were included. The incidence of BSI was 57%. In most cases, multidrug-resistant pathogens were isolated. Dyslipidemia was more frequent in the BSI group (p < 0.05). Moreover, BSI-group patients had a longer ICU stay and a longer duration of both mechanical ventilation and sedation (p < 0.05). Deaths were not statistically different between the two groups (73% for BSI and 56% for the non-BSI group, p > 0.05). Compared with non-survivors, survivors had lower baseline APACHE II and SOFA scores, lower D-dimers levels, a higher baseline compliance of the respiratory system, and less frequent heart failure. They received anakinra less frequently and appropriate therapy more often (p < 0.05). The independent risk factor for mortality was the APACHE II score [1.232 (1.017 to 1.493), p = 0.033]. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
15 pages, 1515 KiB  
Article
The Impact of Antimicrobial Stewardship and Infection Control Interventions on Acinetobacter baumannii Resistance Rates in the ICU of a Tertiary Care Center in Lebanon
by Nesrine A. Rizk, Nada Zahreddine, Nisrine Haddad, Rihab Ahmadieh, Audra Hannun, Souad Bou Harb, Sara F. Haddad, Rony M. Zeenny and Souha S. Kanj
Antibiotics 2022, 11(7), 911; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11070911 - 07 Jul 2022
Cited by 14 | Viewed by 3002
Abstract
Antimicrobial resistance is a serious threat to global health, causing increased mortality and morbidity especially among critically ill patients. This toll is expected to rise following the COVID-19 pandemic. Carbapenem-resistant Acinetobacter baumannii (CRAb) is among the Gram-negative pathogens leading antimicrobial resistance globally; it [...] Read more.
Antimicrobial resistance is a serious threat to global health, causing increased mortality and morbidity especially among critically ill patients. This toll is expected to rise following the COVID-19 pandemic. Carbapenem-resistant Acinetobacter baumannii (CRAb) is among the Gram-negative pathogens leading antimicrobial resistance globally; it is listed as a critical priority pathogen by the WHO and is implicated in hospital-acquired infections and outbreaks, particularly in critically ill patients. Recent reports from Lebanon describe increasing rates of infection with CRAb, hence the need to develop concerted interventions to control its spread. We set to describe the impact of combining antimicrobial stewardship and infection control measures on resistance rates and colonization pressure of CRAb in the intensive care units of a tertiary care center in Lebanon before the COVID-19 pandemic. The antimicrobial stewardship program introduced a carbapenem-sparing initiative in April 2019. During the same period, infection control interventions involved focused screening, monitoring, and tracking of CRAb, as well as compliance with specific measures. From January 2018 to January 2020, we report a statistically significant decrease in carbapenem consumption and a decrease in resistance rates of isolated A. baumannii. The colonization pressure of CRAb also decreased significantly, reaching record low levels at the end of the intervention period. The results indicate that a multidisciplinary approach and combined interventions between the stewardship and infection control teams can lead to a sustained reduction in resistance rates and CRAb spread in ICUs. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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13 pages, 476 KiB  
Article
Clinical Features and Outcomes of Monobacterial and Polybacterial Episodes of Ventilator-Associated Pneumonia Due to Multidrug-Resistant Acinetobacter baumannii
by Dalia Adukauskiene, Ausra Ciginskiene, Agne Adukauskaite, Despoina Koulenti and Jordi Rello
Antibiotics 2022, 11(7), 892; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11070892 - 04 Jul 2022
Cited by 10 | Viewed by 1876
Abstract
Multidrug-resistant A. baumannii (MDRAB) VAP has high morbidity and mortality, and the rates are constantly increasing globally. Mono- and polybacterial MDRAB VAP might differ, including outcomes. We conducted a single-center, retrospective (January 2014–December 2016) study in the four ICUs (12–18–24 beds each) of [...] Read more.
Multidrug-resistant A. baumannii (MDRAB) VAP has high morbidity and mortality, and the rates are constantly increasing globally. Mono- and polybacterial MDRAB VAP might differ, including outcomes. We conducted a single-center, retrospective (January 2014–December 2016) study in the four ICUs (12–18–24 beds each) of a reference Lithuanian university hospital, aiming to compare the clinical features and the 30-day mortality of monobacterial and polybacterial MDRAB VAP episodes. A total of 156 MDRAB VAP episodes were analyzed: 105 (67.5%) were monomicrobial. The 30-day mortality was higher (p < 0.05) in monobacterial episodes: overall (57.1 vs. 37.3%), subgroup with appropriate antibiotic therapy (50.7 vs. 23.5%), and subgroup of XDR A. baumannii (57.3 vs. 36.4%). Monobacterial MDRAB VAP was associated (p < 0.05) with Charlson comorbidity index ≥3 (67.6 vs. 47.1%), respiratory comorbidities (19.0 vs. 5.9%), obesity (27.6 vs. 9.8%), prior hospitalization (58.1 vs. 31.4%), prior antibiotic therapy (99.0 vs. 92.2%), sepsis (88.6 vs. 76.5%), septic shock (51.9 vs. 34.6%), severe hypoxemia (23.8 vs. 7.8%), higher leukocyte count on VAP onset (median [IQR] 11.6 [8.4–16.6] vs. 10.9 [7.3–13.4]), and RRT need during ICU stay (37.1 vs. 17.6%). Patients with polybacterial VAP had a higher frequency of decreased level of consciousness (p < 0.05) on ICU admission (29.4 vs. 14.3%) and on VAP onset (29.4 vs. 11.4%). We concluded that monobacterial MDRAB VAP had different demographic/clinical characteristics compared to polybacterial and carried worse outcomes. These important findings need to be validated in a larger, prospective study, and the management implications to be further investigated. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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12 pages, 595 KiB  
Article
Epidemiology of Candidemia and Fluconazole Resistance in an ICU before and during the COVID-19 Pandemic Era
by Christina Routsi, Joseph Meletiadis, Efstratia Charitidou, Aikaterini Gkoufa, Stelios Kokkoris, Stavros Karageorgiou, Charalampos Giannopoulos, Despoina Koulenti, Petros Andrikogiannopoulos, Efstathia Perivolioti, Athina Argyropoulou, Ioannis Vasileiadis, Georgia Vrioni and Elizabeth Paramythiotou
Antibiotics 2022, 11(6), 771; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11060771 - 04 Jun 2022
Cited by 23 | Viewed by 2193
Abstract
The objectives of this study were to investigate the incidence of candidemia, as well as the factors associated with Candida species distribution and fluconazole resistance, among patients admitted to the intensive care unit (ICU) during the COVID-19 pandemic, as compared to two pre-pandemic [...] Read more.
The objectives of this study were to investigate the incidence of candidemia, as well as the factors associated with Candida species distribution and fluconazole resistance, among patients admitted to the intensive care unit (ICU) during the COVID-19 pandemic, as compared to two pre-pandemic periods. All patients admitted to the ICU due to COVID-19 from March 2020 to October 2021, as well as during two pre-pandemic periods (2005–2008 and 2012–2015), who developed candidemia, were included. During the COVID-19 study period, the incidence of candidemia was 10.2%, significantly higher compared with 3.2% and 4.2% in the two pre-pandemic periods, respectively. The proportion of non-albicans Candida species increased (from 60.6% to 62.3% and 75.8%, respectively), with a predominance of C. parapsilosis. A marked increase in fluconazole resistance (from 31% to 37.7% and 48.4%, respectively) was also observed. Regarding the total patient population with candidemia (n = 205), fluconazole resistance was independently associated with ICU length of stay (LOS) before candidemia (OR 1.03; CI: 1.01–1.06, p = 0.003), whereas the presence of shock at candidemia onset was associated with C. albicans (OR 6.89; CI: 2.2–25, p = 0.001), and with fluconazole-susceptible species (OR 0.23; CI: 0.07–0.64, p = 0.006). In conclusion, substantial increases in the incidence of candidemia, in non-albicansCandida species, and in fluconazole resistance were found in patients admitted to the ICU due to COVID-19, compared to pre-pandemic periods. At candidemia onset, prolonged ICU LOS was associated with fluconazole-resistant and the presence of shock with fluconazole-susceptible species. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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15 pages, 723 KiB  
Article
ICU-Associated Gram-Negative Bloodstream Infection: Risk Factors Affecting the Outcome Following the Emergence of Colistin-Resistant Isolates in a Regional Greek Hospital
by Marios Karvouniaris, Garyphallia Poulakou, Konstantinos Tsiakos, Maria Chatzimichail, Panagiotis Papamichalis, Anna Katsiaflaka, Katerina Oikonomou, Antonios Katsioulis, Eleni Palli and Apostolos Komnos
Antibiotics 2022, 11(3), 405; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030405 - 17 Mar 2022
Cited by 6 | Viewed by 2511
Abstract
Intensive care unit patients may present infections by difficult-to-treat-resistant Gram-negative microorganisms. Colistin resurfaced as a last resort antibiotic for the treatment of multi-drug-resistant Gram-negative bacteria. However, colistin might not improve survival, particularly after the emergence of colistin-resistant isolates. We aimed to (1) examine [...] Read more.
Intensive care unit patients may present infections by difficult-to-treat-resistant Gram-negative microorganisms. Colistin resurfaced as a last resort antibiotic for the treatment of multi-drug-resistant Gram-negative bacteria. However, colistin might not improve survival, particularly after the emergence of colistin-resistant isolates. We aimed to (1) examine the first Gram-negative-associated-bloodstream infection (GN-BSI) effect on 28-day mortality and (2) distinguish mortality risk factors. From 1 January 2018 to 31 December 2019, we retrospectively studied all adult patients admitted for more than 48 h in the critical care department of a regional Greek hospital, with prevalent difficult-to-treat Gram-negative pathogens. We examined the patient records for the first GN-BSI. The local laboratory used broth microdilution to evaluate bacterial susceptibility to colistin. Seventy-eight patients fulfilled the entry criteria: adult and first GN-BSI. They developed GN-BSI on day 10 (6–18), while the overall mortality was 26.9%. Thirty-two and 46 individuals comprised the respective colistin-resistant and colistin-sensitive groups. The admission Acute Physiology Assessment and Chronic Health Evaluation II score was associated with acquiring colistin-resistant GN-BSI in the multivariable logistic regression analysis (οdds ratio (CI), 1.11 (1.03–1.21)). Regarding mortality, the index day sequential organ failure assessment score was solely associated with the outcome (hazard-ratio (CI), 1.23 (1.03–1.48), Cox proportional hazard analysis). GN-BSI was often caused by colistin-resistant bacteria. Concerning our data, sepsis severity was the independent predictor of mortality regardless of the colistin-resistance phenotype or empirical colistin treatment. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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11 pages, 250 KiB  
Article
Size Matters: The Influence of Patient Size on Antibiotics Exposure Profiles in Critically Ill Patients on Continuous Renal Replacement Therapy
by Soo-Min Jang, Alex R. Shaw and Bruce A. Mueller
Antibiotics 2021, 10(11), 1390; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10111390 - 12 Nov 2021
Cited by 4 | Viewed by 1640
Abstract
(1) Purpose of this study: To determine whether patient weight influences the probability of target attainment (PTA) over 72 h of initial therapy with beta-lactam (cefepime, ceftazidime, piperacillin/tazobactam) and carbapenem (imipenem, ertapenem, meropenem) antibiotics in the critical care setting. This is the first [...] Read more.
(1) Purpose of this study: To determine whether patient weight influences the probability of target attainment (PTA) over 72 h of initial therapy with beta-lactam (cefepime, ceftazidime, piperacillin/tazobactam) and carbapenem (imipenem, ertapenem, meropenem) antibiotics in the critical care setting. This is the first paper to address the question of whether patient size affects antibiotic PTA in the ICU. (2) Methods: We performed a post hoc analysis of Monte Carlo simulations conducted in virtual critically ill patients receiving antibiotics and continuous renal replacement therapy. The PTA was calculated for each antibiotic on the following pharmacodynamic (PD) targets: (a) were above the target organism’s minimum inhibitory concentration (≥%fT≥1×MIC), (b) were above four times the MIC (≥%fT≥4×MIC), and (c) were always above the MIC (≥100%fT≥MIC) for the first 72 h of antibiotic therapy. The PTA was analyzed in patient weight quartiles [Q1 (lightest)-Q4 (heaviest)]. Optimal doses were defined as the lowest dose achieving ≥90% PTA. (3) Results: The PTA for fT≥1×MIC led to similarly high rates regardless of weight quartiles. Yet, patient weight influenced the PTA for higher PD targets (100%fT≥MIC and fT≥4×MIC) with commonly used beta-lactams and carbapenems. Reaching the optimal PTA was more difficult with a PD target of 100%fT≥MIC compared to fT≥4×MIC. (4) Conclusions: The Monte Carlo simulations showed patients in lower weight quartiles tended to achieve higher antibiotic pharmacodynamic target attainment compared to heavier patients. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)

Review

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24 pages, 427 KiB  
Review
Current and Potential Therapeutic Options for Infections Caused by Difficult-to-Treat and Pandrug Resistant Gram-Negative Bacteria in Critically Ill Patients
by Helen Giamarellou and Ilias Karaiskos
Antibiotics 2022, 11(8), 1009; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11081009 - 26 Jul 2022
Cited by 17 | Viewed by 3874
Abstract
Carbapenem resistance in Gram-negative bacteria has come into sight as a serious global threat. Carbapenem-resistant Gram-negative pathogens and their main representatives Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are ranked in the highest priority category for new treatments. The worrisome phenomenon [...] Read more.
Carbapenem resistance in Gram-negative bacteria has come into sight as a serious global threat. Carbapenem-resistant Gram-negative pathogens and their main representatives Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa are ranked in the highest priority category for new treatments. The worrisome phenomenon of the recent years is the presence of difficult-to-treat resistance (DTR) and pandrug-resistant (PDR) Gram-negative bacteria, characterized as non-susceptible to all conventional antimicrobial agents. DTR and PDR Gram-negative infections are linked with high mortality and associated with nosocomial infections, mainly in critically ill and ICU patients. Therapeutic options for infections caused by DTR and PDR Gram-negative organisms are extremely limited and are based on case reports and series. Herein, the current available knowledge regarding treatment of DTR and PDR infections is discussed. A focal point of the review focuses on salvage treatment, synergistic combinations (double and triple combinations), as well as increased exposure regimen adapted to the MIC of the pathogen. The most available data regarding novel antimicrobials, including novel β-lactam-β-lactamase inhibitor combinations, cefiderocol, and eravacycline as potential agents against DTR and PDR Gram-negative strains in critically ill patients are thoroughly presented. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
16 pages, 481 KiB  
Review
Antimicrobial Stewardship Using Biomarkers: Accumulating Evidence for the Critically Ill
by Evdoxia Kyriazopoulou and Evangelos J. Giamarellos-Bourboulis
Antibiotics 2022, 11(3), 367; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030367 - 09 Mar 2022
Cited by 10 | Viewed by 3326
Abstract
This review aims to summarize current progress in the management of critically ill, using biomarkers as guidance for antimicrobial treatment with a focus on antimicrobial stewardship. Accumulated evidence from randomized clinical trials (RCTs) and observational studies in adults for the biomarker-guided antimicrobial treatment [...] Read more.
This review aims to summarize current progress in the management of critically ill, using biomarkers as guidance for antimicrobial treatment with a focus on antimicrobial stewardship. Accumulated evidence from randomized clinical trials (RCTs) and observational studies in adults for the biomarker-guided antimicrobial treatment of critically ill (mainly sepsis and COVID-19 patients) has been extensively searched and is provided. Procalcitonin (PCT) is the best studied biomarker; in the majority of randomized clinical trials an algorithm of discontinuation of antibiotics with decreasing PCT over serial measurements has been proven safe and effective to reduce length of antimicrobial treatment, antibiotic-associated adverse events and long-term infectious complications like infections by multidrug-resistant organisms and Clostridioides difficile. Other biomarkers, such as C-reactive protein and presepsin, are already being tested as guidance for shorter antimicrobial treatment, but more research is needed. Current evidence suggests that biomarkers, mainly procalcitonin, should be implemented in antimicrobial stewardship programs even in the COVID-19 era, when, although bacterial coinfection rate is low, antimicrobial overconsumption remains high. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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20 pages, 957 KiB  
Review
Use of Antimicrobials for Bloodstream Infections in the Intensive Care Unit, a Clinically Oriented Review
by Alexis Tabah, Jeffrey Lipman, François Barbier, Niccolò Buetti, Jean-François Timsit and on behalf of the ESCMID Study Group for Infections in Critically Ill Patients—ESGCIP
Antibiotics 2022, 11(3), 362; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030362 - 08 Mar 2022
Cited by 12 | Viewed by 12217
Abstract
Bloodstream infections (BSIs) in critically ill patients are associated with significant mortality. For patients with septic shock, antibiotics should be administered within the hour. Probabilistic treatment should be targeted to the most likely pathogens, considering the source and risk factors for bacterial resistance [...] Read more.
Bloodstream infections (BSIs) in critically ill patients are associated with significant mortality. For patients with septic shock, antibiotics should be administered within the hour. Probabilistic treatment should be targeted to the most likely pathogens, considering the source and risk factors for bacterial resistance including local epidemiology. Source control is a critical component of the management. Sending blood cultures (BCs) and other specimens before antibiotic administration, without delaying them, is key to microbiological diagnosis and subsequent opportunities for antimicrobial stewardship. Molecular rapid diagnostic testing may provide faster identification of pathogens and specific resistance patterns from the initial positive BC. Results allow for antibiotic optimisation, targeting the causative pathogen with escalation or de-escalation as required. Through this clinically oriented narrative review, we provide expert commentary for empirical and targeted antibiotic choice, including a review of the evidence and recommendations for the treatments of extended-spectrum β-lactamase-producing, AmpC-hyperproducing and carbapenem-resistant Enterobacterales; carbapenem-resistant Acinetobacter baumannii; and Staphylococcus aureus. In order to improve clinical outcomes, dosing recommendations and pharmacokinetics/pharmacodynamics specific to ICU patients must be followed, alongside therapeutic drug monitoring. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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17 pages, 1553 KiB  
Review
Empiric Treatment in HAP/VAP: “Don’t You Want to Take a Leap of Faith?”
by Khalil Chaïbi, Gauthier Péan de Ponfilly, Laurent Dortet, Jean-Ralph Zahar and Benoît Pilmis
Antibiotics 2022, 11(3), 359; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030359 - 08 Mar 2022
Cited by 8 | Viewed by 5575
Abstract
Ventilator-associated pneumonia is a frequent cause of ICU-acquired infections. These infections are associated with high morbidity and mortality. The increase in antibiotic resistance, particularly among Gram-negative bacilli, makes the choice of empiric antibiotic therapy complex for physicians. Multidrug-resistant organisms (MDROs) related infections are [...] Read more.
Ventilator-associated pneumonia is a frequent cause of ICU-acquired infections. These infections are associated with high morbidity and mortality. The increase in antibiotic resistance, particularly among Gram-negative bacilli, makes the choice of empiric antibiotic therapy complex for physicians. Multidrug-resistant organisms (MDROs) related infections are associated with a high risk of initial therapeutic inadequacy. It is, therefore, necessary to quickly identify the bacterial species involved and their susceptibility to antibiotics. New diagnostic tools have recently been commercialized to assist in the management of these infections. Moreover, the recent enrichment of the therapeutic arsenal effective on Gram-negative bacilli raises the question of their place in the therapeutic management of these infections. Most national and international guidelines recommend limiting their use to microbiologically documented infections. However, many clinical situations and, in particular, the knowledge of digestive or respiratory carriage by MDROs should lead to the discussion of the use of these new molecules, especially the new combinations with beta-lactamase inhibitors in empirical therapy. In this review, we present the current epidemiological data, particularly in terms of MDRO, as well as the clinical and microbiological elements that may be taken into account in the discussion of empirical antibiotic therapy for patients managed for ventilator-associated pneumonia. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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18 pages, 1743 KiB  
Review
Antibiotics and ECMO in the Adult Population—Persistent Challenges and Practical Guides
by Francisco Gomez, Jesyree Veita and Krzysztof Laudanski
Antibiotics 2022, 11(3), 338; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11030338 - 04 Mar 2022
Cited by 10 | Viewed by 6342
Abstract
Extracorporeal membrane oxygenation (ECMO) is an emerging treatment modality associated with a high frequency of antibiotic use. However, several covariables emerge during ECMO implementation, potentially jeopardizing the success of antimicrobial therapy. These variables include but are not limited to: the increased volume of [...] Read more.
Extracorporeal membrane oxygenation (ECMO) is an emerging treatment modality associated with a high frequency of antibiotic use. However, several covariables emerge during ECMO implementation, potentially jeopardizing the success of antimicrobial therapy. These variables include but are not limited to: the increased volume of distribution, altered clearance, and adsorption into circuit components, in addition to complex interactions of antibiotics in critical care illness. Furthermore, ECMO complicates the assessment of antibiotic effectiveness as fever, or other signs may not be easily detected, the immunogenicity of the circuit affects procalcitonin levels and other inflammatory markers while disrupting the immune system. We provided a review of pharmacokinetics and pharmacodynamics during ECMO, emphasizing practical application and review of patient-, illness-, and ECMO hardware-related factors. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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14 pages, 5831 KiB  
Review
Probiotics in the Intensive Care Unit
by Alex R. Schuurman, Robert F. J. Kullberg and Willem Joost Wiersinga
Antibiotics 2022, 11(2), 217; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11020217 - 08 Feb 2022
Cited by 5 | Viewed by 2754
Abstract
The understanding of the gut microbiome in health and disease has shown tremendous progress in the last decade. Shaped and balanced throughout life, the gut microbiome is intricately related to the local and systemic immune system and a multitude of mechanisms through which [...] Read more.
The understanding of the gut microbiome in health and disease has shown tremendous progress in the last decade. Shaped and balanced throughout life, the gut microbiome is intricately related to the local and systemic immune system and a multitude of mechanisms through which the gut microbiome contributes to the host’s defense against pathogens have been revealed. Similarly, a plethora of negative consequences, such as superinfections and an increased rate of hospital re-admissions, have been identified when the gut microbiome is disturbed by disease or by the iatrogenic effects of antibiotic treatment and other interventions. In this review, we describe the role that probiotics may play in the intensive care unit (ICU). We discuss what is known about the gut microbiome of the critically ill, and the concept of probiotic intervention to positively modulate the gut microbiome. We summarize the evidence derived from randomized clinical trials in this context, with a focus on the prevention of ventilator-associated pneumonia. Finally, we consider what lessons we can learn in terms of the current challenges, efficacy and safety of probiotics in the ICU and what we may expect from the future. Throughout the review, we highlight studies that have provided conceptual advances to the field or have revealed a specific mechanism; this narrative review is not intended as a comprehensive summary of the literature. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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9 pages, 890 KiB  
Perspective
Why We May Need Higher Doses of Beta-Lactam Antibiotics: Introducing the ‘Maximum Tolerable Dose’
by Sofie A. M. Dhaese, Eric A. Hoste and Jan J. De Waele
Antibiotics 2022, 11(7), 889; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11070889 - 04 Jul 2022
Cited by 9 | Viewed by 1976
Abstract
The surge in antimicrobial resistance and the limited availability of new antimicrobial drugs has fueled the interest in optimizing antibiotic dosing. An ideal dosing regimen leads to maximal bacterial cell kill, whilst minimizing the risk of toxicity or antimicrobial resistance. For beta-lactam antibiotics [...] Read more.
The surge in antimicrobial resistance and the limited availability of new antimicrobial drugs has fueled the interest in optimizing antibiotic dosing. An ideal dosing regimen leads to maximal bacterial cell kill, whilst minimizing the risk of toxicity or antimicrobial resistance. For beta-lactam antibiotics specifically, PK/PD-based considerations have led to the widespread adoption of prolonged infusion. The rationale behind prolonged infusion is increasing the percentage of time the beta-lactam antibiotic concentration remains above the minimal inhibitory concentration (%fT>MIC). The ultimate goal of prolonged infusion of beta-lactam antibiotics is to improve the outcome of infectious diseases. However, merely increasing target attainment (or the %fT>MIC) is unlikely to lead to improved clinical outcome for several reasons. First, the PK/PD index and target are dynamic entities. Changing the PK (as is the case if prolonged instead of intermittent infusion is used) will result in different PK/PD targets and even PK/PD indices necessary to obtain the same level of bacterial cell kill. Second, the minimal inhibitory concentration is not a good denominator to describe either the emergence of resistance or toxicity. Therefore, we believe a different approach to antibiotic dosing is necessary. In this perspective, we introduce the concept of the maximum tolerable dose (MTD). This MTD is the highest dose of an antimicrobial drug deemed safe for the patient. The goal of the MTD is to maximize bacterial cell kill and minimize the risk of antimicrobial resistance and toxicity. Unfortunately, data about what beta-lactam antibiotic levels are associated with toxicity and how beta-lactam antibiotic toxicity should be measured are limited. This perspective is, therefore, a plea to invest in research aimed at deciphering the dose–response relationship between beta-lactam antibiotic drug concentrations and toxicity. In this regard, we provide a theoretical approach of how increasing uremic toxin concentrations could be used as a quantifiable marker of beta-lactam antibiotic toxicity. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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24 pages, 864 KiB  
Systematic Review
Systematic Review of Antimicrobial Combination Options for Pandrug-Resistant Acinetobacter baumannii
by Stamatis Karakonstantis, Petros Ioannou, George Samonis and Diamantis P. Kofteridis
Antibiotics 2021, 10(11), 1344; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10111344 - 03 Nov 2021
Cited by 33 | Viewed by 5882
Abstract
Antimicrobial combinations are at the moment the only potential treatment option for pandrug-resistant A. baumannii. A systematic review was conducted in PubMed and Scopus for studies reporting the activity of antimicrobial combinations against A. baumannii resistant to all components of the combination. [...] Read more.
Antimicrobial combinations are at the moment the only potential treatment option for pandrug-resistant A. baumannii. A systematic review was conducted in PubMed and Scopus for studies reporting the activity of antimicrobial combinations against A. baumannii resistant to all components of the combination. The clinical relevance of synergistic combinations was assessed based on concentrations achieving synergy and PK/PD models. Eighty-four studies were retrieved including 818 eligible isolates. A variety of combinations (n = 141 double, n = 9 triple) were tested, with a variety of methods. Polymyxin-based combinations were the most studied, either as double or triple combinations with cell-wall acting agents (including sulbactam, carbapenems, glycopeptides), rifamycins and fosfomycin. Non-polymyxin combinations were predominantly based on rifampicin, fosfomycin, sulbactam and avibactam. Several combinations were synergistic at clinically relevant concentrations, while triple combinations appeared more active than the double ones. However, no combination was consistently synergistic against all strains tested. Notably, several studies reported synergy but at concentrations unlikely to be clinically relevant, or the concentration that synergy was observed was unclear. Selecting the most appropriate combinations is likely strain-specific and should be guided by in vitro synergy evaluation. Furthermore, there is an urgent need for clinical studies on the efficacy and safety of such combinations. Full article
(This article belongs to the Special Issue Antimicrobial Therapy in Intensive Care Unit)
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