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Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Emergency Medicine".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 63455

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Special Issue Editor

Dr. Erlangga Yusuf

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Guest Editor

Department of Medical Microbiology and Infectious Diseases, Erasmus University of Rotterdam, Rotterdam, The Netherlands
Interests: surgical site infection; prosthetic and foreign-material-related infection; diagnostic microbiology; antimicrobial stewardship
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Critically ill patients are at increased risk of having infections. A European Prevalence of infection in intensive Care II (EPIC II) study showed that 51% of all patients were infected and 71% were receiving antibiotics. Research in the diagnostics and treatment of critically ill patients does not stand still. For example, a new definition of sepsis was introduced by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine in 2016. Moreover, several challenges remain, such as when to start antibiotics since half of febrile events in critically ill patients do not have infectious origins. When to stop the antibiotic is also often the question, since microbiology diagnostics is not always positive.

This Special Issue calls for papers regarding the diagnostics and antibiotic treatment of infections in critically ill patients. Infection prevention studies such as care bundle in intensive care are also welcomed.

We are very interested in updated reviews regarding diagnostic and antimicrobial treatment of common infectious problems in critically ill patients, such as ventilator-associated pneumonia, intraabdominal infection, and catheter-associated urinary tract infections. Less common infections such as mediastinitis and skin and soft tissue infection in this specific patient group will also be considered.

We will gladly review studies on innovation, such as new diagnostics (e.g., rapid molecular tests (PCRs), procalcitonin) in clinical decision making, and the use of big data in intensive care medicine. Studies on new antibiotic treatment for multidrug resistant microorganisms (e.g., ceftazidim/avibactam, ceftarolin, or revitalized antibiotics, such as colistin), such as studies on antifungal treatment of invasive fungal infection will be considered for publication.

You can submit narrative and systematic reviews, RCTs, descriptive, and observational studies. Only when a case is unique and has important educational value will we accept case reports for peer review.

Dr. Erlangga Yusuf
Guest Editor

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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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

Critical ill patients
Intensive care
Antimicrobial treatment
Antifungal therapy
Microbiology diagnostic
Blood stream infection
Invasive fungal infections
Ventilator associated pneumonia
Intraabdominal infection
Complicated urinary tract infection
New antibiotics
Infection prevention
Epidemiology
Big data

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

3 pages, 190 KiB

Open AccessEditorial

Valid Evidence for Diagnosis and Treatment of Infections in the Intensive Care Unit: Beyond Randomized Control Trial Study Design (Trial Emulation and Machine Learning)

by Erlangga Yusuf and Frits R. Rosendaal

J. Clin. Med. 2022, 11(13), 3600; https://doi.org/10.3390/jcm11133600 - 22 Jun 2022

Viewed by 1057

Abstract

Infection in critically ill patients is an important problem [...] Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

Research

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10 pages, 640 KiB

Open AccessArticle

Impact of Invasive Fungal Diseases on Survival under Veno-Venous Extracorporeal Membrane Oxygenation for ARDS

by Jens Martin Poth, Jens-Christian Schewe, Christian Putensen and Stefan Felix Ehrentraut

J. Clin. Med. 2022, 11(7), 1940; https://doi.org/10.3390/jcm11071940 - 31 Mar 2022

Cited by 13 | Viewed by 2435

Abstract

Objective: To assess the incidence and significance of invasive fungal diseases (IFD) during veno-venous (VV) ECMO support for acute respiratory distress syndrome (ARDS). Methods: Retrospective analysis from January 2013 to April 2021 of all ECMO cases for ARDS at a German University Hospital. In patients with IFD (IFD patients), type of IFD, time of IFD, choice of antifungal agent, duration, and success of therapy were investigated. For comparison, patients without IFD (non-IFD patients) were selected by propensity score matching using treatment-independent variables (age, gender, height, weight, and the Sequential Organ Failure Assessment (SOFA) score at ICU admission). Demographics, hospital and ICU length of stay, duration of ECMO therapy, days on mechanical ventilation, prognostic scores (Charlson Comorbidity Index (CCI), Therapeutic Intervention Scoring System (TISS), and length of survival were assessed. Results: A total of 646 patients received ECMO, 368 patients received VV ECMO. The incidence of IFD on VV ECMO was 5.98%, with 5.43% for Candida bloodstream infections (CBSI) and 0.54% for invasive aspergillosis (IA). In IFD patients, in-hospital mortality was 81.8% versus 40.9% in non-IFD patients. The hazard ratio for death was 2.5 (CI 1.1–5.4; p: 0.023) with IFD. Conclusions: In patients on VV ECMO for ARDS, about one in 17 contracts an IFD, with a detrimental impact on prognosis. Further studies are needed to address challenges in the diagnosis and treatment of IFD in this population. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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12 pages, 1352 KiB

Open AccessArticle

Compared the Microbiota Profiles between Samples from Bronchoalveolar Lavage and Endotracheal Aspirates in Severe Pneumonia: A Real-World Experience

by Yeong-Nan Cheng, Wei-Chih Huang, Chen-Yu Wang and Pin-Kuei Fu

J. Clin. Med. 2022, 11(2), 327; https://doi.org/10.3390/jcm11020327 - 10 Jan 2022

Cited by 3 | Viewed by 1878

Abstract

Lower respiratory tract sampling from endotracheal aspirate (EA) and bronchoalveolar lavage (BAL) are both common methods to identify pathogens in severe pneumonia. However, the difference between these two methods in microbiota profiles remains unclear. We compared the microbiota profiles of pairwise EA and BAL samples in ICU patients with respiratory failure due to severe pneumonia. We prospectively enrolled 50 ICU patients with new onset of pneumonia requiring mechanical ventilation. EA and BAL were performed on the first ICU day, and samples were analyzed for microbial community composition via 16S rRNA metagenomic sequencing. Pathogens were identified in culture medium from BAL samples in 21 (42%) out of 50 patients. No difference was observed in the antibiotic prescription pattern, ICU mortality, or hospital mortality between BAL-positive and BAL-negative patients. The microbiota profiles in the EA and BAL samples are similar with respect to diversity, microbial composition, and microbial community correlations. The antibiotic treatment regimen was rarely changed based on the BAL findings. The samples from BAL did not provide more information than EA in the microbiota profiles. We suggest that EA is more useful than BAL for microbiome identification in mechanically ventilated patients. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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7 pages, 239 KiB

Open AccessArticle

Antibiotic De-escalation Experience in the Setting of Emergency Department: A Retrospective, Observational Study

by Silvia Corcione, Simone Mornese Pinna, Tommaso Lupia, Alice Trentalange, Erika Germanò, Rossana Cavallo, Enrico Lupia and Francesco Giuseppe De Rosa

J. Clin. Med. 2021, 10(15), 3285; https://doi.org/10.3390/jcm10153285 - 26 Jul 2021

Cited by 5 | Viewed by 2333

Abstract

Background: Antimicrobial de-escalation (ADE) is a part of antimicrobial stewardship strategies aiming to minimize unnecessary or inappropriate antibiotic exposure to decrease the rate of antimicrobial resistance. Information regarding the effectiveness and safety of ADE in the setting of emergency medicine wards (EMW) is lacking. Methods: Adult patients admitted to EMW and receiving empiric antimicrobial treatment were retrospectively studied. The primary outcome was the rate and timing of ADE. Secondary outcomes included factors associated with early ADE, length of stay, and in-hospital mortality. Results: A total of 336 patients were studied. An initial regimen combining two agents was prescribed in 54.8%. Ureidopenicillins and carbapenems were the most frequently empiric treatment prescribed (25.1% and 13.6%). The rate of the appropriateness of prescribing was 58.3%. De-escalation was performed in 111 (33%) patients. Patients received a successful de-escalation on day 2 (21%), 3 (23%), and 5 (56%). The overall in-hospital mortality was 21%, and it was significantly lower among the de-escalation group than the continuation group (16% vs 25% p = 0.003). In multivariate analysis, de-escalation strategies as well as appropriate empiric and targeted therapy were associated with reduced mortality. Conclusions: ADE appears safe and effective in the setting of EMWs despite that further research is warranted to confirm these findings. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

13 pages, 620 KiB

Open AccessArticle

Incidence and Prognosis of Ventilator-Associated Pneumonia in Critically Ill Patients with COVID-19: A Multicenter Study

by Daniele Roberto Giacobbe, Denise Battaglini, Elisa Martina Enrile, Chiara Dentone, Antonio Vena, Chiara Robba, Lorenzo Ball, Michele Bartoletti, Irene Coloretti, Stefano Di Bella, Antonio Di Biagio, Iole Brunetti, Malgorzata Mikulska, Novella Carannante, Andrea De Maria, Laura Magnasco, Alberto Enrico Maraolo, Michele Mirabella, Giorgia Montrucchio, Nicolò Patroniti, Lucia Taramasso, Giusy Tiseo, Giacomo Fornaro, Fiorentino Fraganza, Luca Monastra, Erik Roman-Pognuz, Giacomo Paluzzano, Giuseppe Fiorentino, Antonio Corcione, Linda Bussini, Renato Pascale, Silvia Corcione, Tommaso Tonetti, Matteo Rinaldi, Marco Falcone, Emanuela Biagioni, Vito Marco Ranieri, Maddalena Giannella, Francesco Giuseppe De Rosa, Massimo Girardis, Francesco Menichetti, Pierluigi Viale, Paolo Pelosi and Matteo Bassetti Show full author list Hide full author list

J. Clin. Med. 2021, 10(4), 555; https://doi.org/10.3390/jcm10040555 - 3 Feb 2021

Cited by 90 | Viewed by 12360

Abstract

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16–21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were Pseudomonas aeruginosa (27/77, 35%) and Staphylococcus aureus (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43–7.61, p = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05–57.26, p < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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9 pages, 777 KiB

Open AccessArticle

Antimicrobial Stewardship Program, COVID-19, and Infection Control: Spread of Carbapenem-Resistant Klebsiella Pneumoniae Colonization in ICU COVID-19 Patients. What Did Not Work?

by Beatrice Tiri, Emanuela Sensi, Viola Marsiliani, Mizar Cantarini, Giulia Priante, Carlo Vernelli, Lucia Assunta Martella, Monya Costantini, Alessandro Mariottini, Paolo Andreani, Paolo Bruzzone, Fabio Suadoni, Marsilio Francucci, Roberto Cirocchi and Stefano Cappanera

J. Clin. Med. 2020, 9(9), 2744; https://doi.org/10.3390/jcm9092744 - 25 Aug 2020

Cited by 155 | Viewed by 8290

Abstract

The Italian burden of disease associated with infections due to antibiotic-resistant bacteria has been very high, largely attributed to Carbapenem-Resistant Klebsiella pneumoniae (CR-Kp). The implementation of infection control measures and antimicrobial stewardship programs (ASP) has been shown to reduce healthcare-related infections caused by multidrug resistance (MDR) germs. Since 2016, in our teaching hospital of Terni, an ASP has been implemented in an intensive care unit (ICU) setting, with the “daily-ICU round strategy” and particular attention to infection control measures. We performed active surveillance for search patients colonized by Carbapenem-Resistant Enterobacteriaceae (CRE). In March 2020, coronavirus disease 2019 (COVID-19) arrived and the same ICU was reserved only for COVID-19 patients. In our retrospective observational study, we analyzed the bimonthly incidence of CRE colonization patients and the incidence of CRE acquisition in our ICU during the period of January 2019 to June 2020. In consideration of the great attention and training of all staff on infection control measures in the COVID-19 era, we would have expected a clear reduction in CRE acquisition, but this did not happen. In fact, the incidence of CRE acquisition went from 6.7% in 2019 to 50% in March–April 2020. We noted that 67% of patients that had been changed in posture with prone position were colonized by CRE, while only 37% of patients that had not been changed in posture were colonized by CRE. In our opinion, the high intensity of care, the prone position requiring 4–5 healthcare workers (HCWs), equipped with personal protective equipment (PPE) in a high risk area, with extended and prolonged contact with the patient, and the presence of 32 new HCWs from other departments and without work experience in the ICU setting, contributed to the spread of CR-Kp in our ICU, determining an increase in CRE acquisition colonization. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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12 pages, 1348 KiB

Open AccessArticle

The Hypotension Period after Initiation of Appropriate Antimicrobial Administration Is Crucial for Survival of Bacteremia Patients Initially Experiencing Severe Sepsis and Septic Shock

by Ching-Chi Lee, Chao-Yung Yang, Bo-An Su, Chih-Chia Hsieh, Ming-Yuan Hong, Chung-Hsun Lee and Wen-Chien Ko

J. Clin. Med. 2020, 9(8), 2617; https://doi.org/10.3390/jcm9082617 - 12 Aug 2020

Cited by 2 | Viewed by 2331

Abstract

Bacteremia is linked to substantial morbidity and medical costs. However, the association between the timing of achieving hemodynamic stability and clinical outcomes remains undetermined. Of the multicenter cohort consisted of 888 adults with community-onset bacteremia initially complicated with severe sepsis and septic shock in the emergency department (ED), a positive linear-by-linear association (γ = 0.839, p < 0.001) of the time-to-appropriate antibiotic (TtAa) and the hypotension period after appropriate antimicrobial therapy (AAT) was exhibited, and a positive trend of the hypotension period after AAT administration in the 15-day (γ = 0.957, p = 0.003) or 30-day crude (γ = 0.975, p = 0.001) mortality rate was evidenced. Moreover, for every hour delay of the TtAa, 30-day survival dropped an average of 0.8% (adjusted odds ratio [AOR], 1.008; p < 0.001); and each additional hour of the hypotension period following AAT initiation notably resulted in with an average 1.1% increase (AOR, 1.011; p < 0.001) in the 30-day crude mortality rate, after adjusting all independent determinants of 30-day mortality recognized by the multivariate regression model. Conclusively, for bacteremia patients initially experiencing severe sepsis and septic shock, prompt AAT administration might shorten the hypotension period to achieve favourable prognoses. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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10 pages, 981 KiB

Open AccessArticle

Mortality After Delay of Adequate Empiric Antimicrobial Treatment of Bloodstream Infection

by Merel M. C. Lambregts, Roos Wijnakker, Alexandra T. Bernards, Leo G. Visser, Saskia le Cessie and Mark G. J. de Boer

J. Clin. Med. 2020, 9(5), 1378; https://doi.org/10.3390/jcm9051378 - 7 May 2020

Cited by 11 | Viewed by 2825

Abstract

Background: Timely empiric antimicrobial therapy is one of the cornerstones of the management of suspected bloodstream infection (BSI). However, studies about the effects of empiric therapy on mortality have reported inconsistent results. The objective of this study was to estimate the effect of delay of appropriate empiric therapy on early mortality in patients with BSI. Methods: Data for the propensity score matching (PSM) study were obtained from a cohort of patients with BSI. Inadequate empiric treatment was defined as in vitro resistance to the antimicrobial regimen administered <6 h after blood cultures were taken. The primary outcome measure was 14-day mortality. Thirty-day mortality and median length of stay (LOS) were secondary outcomes. PSM was applied to control for confounding. Results: Of a total of 893 included patients with BSI, 35.7% received inadequate initial empiric treatment. In the PSM cohort (n = 334), 14-day mortality was 9.6% for inadequate antibiotic treatment, compared to. 10.2% in adequate empiric treatment (p = 0.85). No prolonged median LOS was observed in patients who initially received inadequate therapy (10.5 vs. 10.7 days, p = 0.89). Conclusions: In this study, we found no clear effect of inadequate empirical treatment on mortality in a low-risk BSI population. The importance of early empiric therapy compared to other determinants, may be limited. This may not apply for specific subpopulations, e.g., patients with sepsis. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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14 pages, 1201 KiB

Open AccessArticle

Linezolid Concentrations in Plasma and Subcutaneous Tissue are Reduced in Obese Patients, Resulting in a Higher Risk of Underdosing in Critically Ill Patients: A Controlled Clinical Pharmacokinetic Study

by Philipp Simon, David Busse, David Petroff, Christoph Dorn, Lisa Ehmann, Sophie Hochstädt, Felix Girrbach, Arne Dietrich, Markus Zeitlinger, Frieder Kees, Charlotte Kloft and Hermann Wrigge

J. Clin. Med. 2020, 9(4), 1067; https://doi.org/10.3390/jcm9041067 - 9 Apr 2020

Cited by 18 | Viewed by 5280

Abstract

Background: Linezolid is used for the treatment of soft tissue infections in critically ill patients. However, data for characterizing the pharmacokinetics (PK) and assessing whether effective concentrations are reached at the target site are lacking. We hypothesized that current dosing regimens do not lead to effective concentrations in the plasma and interstitial fluid (ISF) of subcutaneous tissue in obese patients. Methods: As a controlled clinical model, critically ill obese and non-obese patients undergoing intra-abdominal surgery received 600 mg linezolid as a single infusion. Concentrations in the plasma and microdialysate from the ISF of subcutaneous tissue were determined up to 8 h after dosing. Pharmacokinetic analysis was performed by non-compartmental methods. As a therapeutic target, we used fAUC/MIC > 80. Results: Fifteen obese (BMI: 48.7 ± 11.2 kg/m²) and 15 non-obese (23.9 ± 2.1 kg/m²) patients were analyzed. AUC_0–8 in ISF decreased by −1.69 mg*h/L (95% CI: −2.59 to −0.79, p < 0.001) for every 10 kg increase in weight. PK in obese patients were characterized by lower maximal plasma concentrations (median 3.8 vs. 8.3 mg/L, p < 0.001) and a higher volume of distribution (41.0 vs. 30.8 L, p < 0.001), and the therapeutic target was not reached for MIC ≥ 1 mg/L in ISF and ≥ 2 mg/L in plasma. Conclusions: Increasing the weight led to a decrease of linezolid concentrations in the plasma and subcutaneous tissue. The current dosing regimen does not seem to produce sufficient concentrations to kill bacteria with MIC ≥ 2 mg/L, especially as empirical antimicrobial therapy in critically ill obese patients. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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Review

Jump to: Editorial, Research

14 pages, 441 KiB

Open AccessReview

Aspergillus in Critically Ill COVID-19 Patients: A Scoping Review

by Erlangga Yusuf, Leonard Seghers, Rogier A. S. Hoek, Johannes P. C. van den Akker, Lonneke G. M. Bode and Bart J. A. Rijnders

J. Clin. Med. 2021, 10(11), 2469; https://doi.org/10.3390/jcm10112469 - 2 Jun 2021

Cited by 13 | Viewed by 3015

Abstract

Several reports have been published on Aspergillus findings in COVID-19 patients leading to a proposition of new disease entity COVID-19-associated pulmonary aspergillosis. This scoping review is designed at clarifying the concepts on how the findings of Aspergillus spp. in COVID-19 patients were interpreted. We searched Medline to identify the studies on Aspergillus spp. findings in COVID-19 patients. Included were observational studies containing the following information: explicit mention of the total number of the study population, study period, reason for obtaining respiratory samples, case definition, and clinical outcomes. Excluded were case series, case reports and reviews. Identified were 123 publications, and 8 observational studies were included. From the included studies the following issues were identified. The proportion of immunocompromised patients considered as host factors varied from 0 to 17%. Most of the studies did not mention radiographic findings explicitly. Respiratory samples were mostly obtained to investigate clinical deterioration. Aspergillus culture, antigen or PCR testing on bronchoalveolar lavage (BAL) fluid were performed in between 23.3% and 66.3% of the study population. Two studies performed periodic samples of BAL. Galactomannan index (GI) positivity in BAL was between 10% and 28%. GI in blood was found in 0.9% to 6.7% of the available samples. The prevalence of COVID-19-associated pulmonary aspergillosis ranged from 2.7% to 27.7%. Studies compared the mortality between defined cases and non-cases, and all showed increased mortality in cases. No studies showed that antifungal treatment reduced mortality. Concluding, this review showed how studies defined the clinical entity COVID-19-associated pulmonary aspergillosis where positive Aspergillus test in the respiratory sample was the main driver for the diagnosis. There were many differences between studies in terms of test algorithm and Aspergillus test used that largely determined the prevalence. Whether antifungal therapy, either as prophylaxis, pre-emptive or targeted therapy will lead to better outcomes of COVID-19-associated pulmonary aspergillosis patients is still need to be answered. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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20 pages, 330 KiB

Open AccessReview

New-Generation Antibiotics for Treatment of Gram-Positive Infections: A Review with Focus on Endocarditis and Osteomyelitis

by Annemieke Bloem, Hannelore I. Bax, Erlangga Yusuf and Nelianne J. Verkaik

J. Clin. Med. 2021, 10(8), 1743; https://doi.org/10.3390/jcm10081743 - 17 Apr 2021

Cited by 27 | Viewed by 7614

Abstract

Infective endocarditis, osteomyelitis, and osteosynthesis-associated infections are mostly caused by Gram-positive bacteria. They are often difficult to treat and are associated with a poor prognosis. In the past 20 years, nine antibiotic drugs with predominant activity against Gram-positive bacteria have been introduced and approved by the Food and Drug Administration or the European Medicines Agency: ceftaroline, daptomycin, telavancin, dalbavancin, oritavancin, linezolid, tedizolid, delafloxacin, and omadacycline. This narrative review aims to provide an overview on these antibiotics with a special focus on their use in infective endocarditis, osteomyelitis, and osteosynthesis-associated infections. Although some of these approved antibiotics are promising, they should not be used as first- or second-line therapy, awaiting more clinical data. Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

17 pages, 336 KiB

Open AccessReview

An Update on Eight “New” Antibiotics against Multidrug-Resistant Gram-Negative Bacteria

by Erlangga Yusuf, Hannelore I. Bax, Nelianne J. Verkaik and Mireille van Westreenen

J. Clin. Med. 2021, 10(5), 1068; https://doi.org/10.3390/jcm10051068 - 4 Mar 2021

Cited by 62 | Viewed by 12630

Abstract

Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam). Full article

(This article belongs to the Special Issue Update on Diagnostic, Antibiotic Treatment, and Prevention of Infections in Critically Ill Patients)

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