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Open AccessEditorial

Multidrug Resistance in Critically Ill Patients: An Unresolved Issue

by Savino Spadaro

Microorganisms 2023, 11(4), 946; https://doi.org/10.3390/microorganisms11040946 - 4 Apr 2023

Cited by 1 | Viewed by 955

Abstract

Sepsis and septic shock are common in critically ill patients and, as recommended by the Surviving Sepsis Campaign (SSC), early empiric antimicrobial therapy, specifically within the first hour, is crucial for the successful management of these conditions. To be effective, the antimicrobial therapy [...] Read more.

Sepsis and septic shock are common in critically ill patients and, as recommended by the Surviving Sepsis Campaign (SSC), early empiric antimicrobial therapy, specifically within the first hour, is crucial for the successful management of these conditions. To be effective, the antimicrobial therapy must also be appropriately administered: the drugs should cover the most probable pathogens and achieve effective concentrations at the site of infection. However, pharmacokinetics are frequently altered in critically ill patients and continuously change since the clinical conditions of these patients quickly and markedly change over time, either improving or deteriorating. Accordingly, optimizing antimicrobial drug dosing is fundamental in intensive care units (ICUs). This Special Issue of Microorganisms examines the epidemiology, diagnostic innovations, and strategies applied in the context of infections in critically ill patients with MDR infections. Full article

(This article belongs to the Special Issue Complex Infectious Issues in Critically Ill Patients)

Research

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13 pages, 1223 KiB

Open AccessArticle

A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation

by Ruth Van Daele, Britt Bekkers, Mattias Lindfors, Lars Mikael Broman, Alexander Schauwvlieghe, Bart Rijnders, Nicole G. M. Hunfeld, Nicole P. Juffermans, Fabio Silvio Taccone, Carlos Antônio Coimbra Sousa, Luc-Marie Jacquet, Pierre-François Laterre, Eric Nulens, Veerle Grootaert, Haifa Lyster, Anna Reed, Brijesh Patel, Philippe Meersseman, Yves Debaveye, Joost Wauters, Christophe Vandenbriele and Isabel Spriet Show full author list Hide full author list

Microorganisms 2021, 9(7), 1543; https://doi.org/10.3390/microorganisms9071543 - 20 Jul 2021

Cited by 24 | Viewed by 3458

Abstract

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. Methods: [...] Read more.

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit’s binding sites over time. Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2–4.7) mg/L under ECMO and 2.5 (1.4–3.9) mg/L without ECMO (p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations. Full article

(This article belongs to the Special Issue Complex Infectious Issues in Critically Ill Patients)

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12 pages, 1527 KiB

Open AccessEditor’s ChoiceArticle

Meropenem Pharmacokinetics and Target Attainment in Critically Ill Patients Are Not Affected by Extracorporeal Membrane Oxygenation: A Matched Cohort Analysis

by Matthias Gijsen, Erwin Dreesen, Pieter Annaert, Johan Nicolai, Yves Debaveye, Joost Wauters and Isabel Spriet

Microorganisms 2021, 9(6), 1310; https://doi.org/10.3390/microorganisms9061310 - 16 Jun 2021

Cited by 14 | Viewed by 3931

Abstract

Existing evidence is inconclusive whether meropenem dosing should be adjusted in patients receiving extracorporeal membrane oxygenation (ECMO). Therefore, the aim of this observational matched cohort study was to evaluate the effect of ECMO on pharmacokinetic (PK) variability and target attainment (TA) of meropenem. [...] Read more.

Existing evidence is inconclusive whether meropenem dosing should be adjusted in patients receiving extracorporeal membrane oxygenation (ECMO). Therefore, the aim of this observational matched cohort study was to evaluate the effect of ECMO on pharmacokinetic (PK) variability and target attainment (TA) of meropenem. Patients admitted to the intensive care unit (ICU) simultaneously treated with meropenem and ECMO were eligible. Patients were matched 1:1, based on renal function and body weight, with non-ECMO ICU patients. Meropenem blood sampling was performed over one or two dosing intervals. Population PK modelling was performed using NONMEM7.5. TA was defined as free meropenem concentrations >2 or 8 mg/L (i.e., 1 or 4× minimal inhibitory concentration, respectively) throughout the whole dosing interval. In total, 25 patients were included, contributing 27 dosing intervals. The overall TA was 56% and 26% for the 2 mg/L and 8 mg/L target, respectively. Population PK modelling identified estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology equation and body weight, but not ECMO, as significant predictors. In conclusion, TA of meropenem was confirmed to be poor under standard dosing in critically ill patients but was not found to be influenced by ECMO. Future studies should focus on applying dose optimisation strategies for meropenem based on renal function, regardless of ECMO. Full article

(This article belongs to the Special Issue Complex Infectious Issues in Critically Ill Patients)

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11 pages, 916 KiB

Open AccessArticle

The Acquisition of Multidrug-Resistant Bacteria in Patients Admitted to COVID-19 Intensive Care Units: A Monocentric Retrospective Case Control Study

by Elisa G. Bogossian, Fabio S. Taccone, Antonio Izzi, Nicolas Yin, Alessandra Garufi, Stephane Hublet, Hassane Njimi, Amedee Ego, Julie Gorham, Baudouin Byl, Alexandre Brasseur, Maya Hites, Jean-Louis Vincent, Jacques Creteur and David Grimaldi

Microorganisms 2020, 8(11), 1821; https://doi.org/10.3390/microorganisms8111821 - 19 Nov 2020

Cited by 23 | Viewed by 3191

Abstract

Whether the risk of multidrug-resistant bacteria (MDRB) acquisition in the intensive care unit (ICU) is modified by the COVID-19 crisis is unknown. In this single center case control study, we measured the rate of MDRB acquisition in patients admitted in COVID-19 ICU and [...] Read more.

Whether the risk of multidrug-resistant bacteria (MDRB) acquisition in the intensive care unit (ICU) is modified by the COVID-19 crisis is unknown. In this single center case control study, we measured the rate of MDRB acquisition in patients admitted in COVID-19 ICU and compared it with patients admitted in the same ICU for subarachnoid hemorrhage (controls) matched 1:1 on length of ICU stay and mechanical ventilation. All patients were systematically and repeatedly screened for MDRB carriage. We compared the rate of MDRB acquisition in COVID-19 patients and in control using a competing risk analysis. Of note, although we tried to match COVID-19 patients with septic shock patients, we were unable due to the longer stay of COVID-19 patients. Among 72 patients admitted to the COVID-19 ICUs, 33% acquired 31 MDRB during ICU stay. The incidence density of MDRB acquisition was 30/1000 patient days. Antimicrobial therapy and exposure time were associated with higher rate of MDRB acquisition. Among the 72 SAH patients, 21% acquired MDRB, with an incidence density was 18/1000 patient days. The septic patients had more comorbidities and a greater number of previous hospitalizations than the COVID-19 patients. The incidence density of MDRB acquisition was 30/1000 patient days. The association between COVID-19 and MDRB acquisition (compared to control) risk did not reach statistical significance in the multivariable competing risk analysis (sHR 1.71 (CI 95% 0.93–3.21)). Thus, we conclude that, despite strong physical isolation, acquisition rate of MDRB in ICU patients was at least similar during the COVID-19 first wave compared to previous period. Full article

(This article belongs to the Special Issue Complex Infectious Issues in Critically Ill Patients)

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Review

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14 pages, 531 KiB

Open AccessReview

Multi-Drug Resistance Bacterial Infections in Critically Ill Patients Admitted with COVID-19

by Daniela Pasero, Andrea Pasquale Cossu and Pierpaolo Terragni

Microorganisms 2021, 9(8), 1773; https://doi.org/10.3390/microorganisms9081773 - 20 Aug 2021

Cited by 37 | Viewed by 3923

Abstract

Introduction. It is known that bacterial infections represent a common complication during viral respiratory tract infections such as influenza, with a concomitant increase in morbidity and mortality. Nevertheless, the prevalence of bacterial co-infections and secondary infections in critically ill patients affected by coronavirus [...] Read more.

Introduction. It is known that bacterial infections represent a common complication during viral respiratory tract infections such as influenza, with a concomitant increase in morbidity and mortality. Nevertheless, the prevalence of bacterial co-infections and secondary infections in critically ill patients affected by coronavirus disease 2019 (COVID-19) is not well understood yet. We performed a review of the literature currently available to examine the incidence of bacterial secondary infections acquired during hospital stay and the risk factors associated with multidrug resistance. Most of the studies, mainly retrospective and single-centered, highlighted that the incidence of co-infections is low, affecting about 3.5% of hospitalized patients, while the majority are hospital acquired infections, developed later, generally 10–15 days after ICU admission. The prolonged ICU hospitalization and the extensive use of broad-spectrum antimicrobial drugs during the COVID-19 outbreak might have contributed to the selection of pathogens with different profiles of resistance. Consequently, the reported incidence of MDR bacterial infections in critically ill COVID-19 patients is high, ranging between 32% to 50%. MDR infections are linked to a higher length of stay in ICU but not to a higher risk of death. The only risk factor independently associated with MDR secondary infections reported was invasive mechanical ventilation (OR 1.062; 95% CI 1.012–1.114), but also steroid therapy and prolonged length of ICU stay may play a pivotal role. The empiric antimicrobial therapy for a ventilated patient with suspected or proven bacterial co-infection at ICU admission should be prescribed judiciously and managed according to a stewardship program in order to interrupt or adjust it on the basis of culture results. Full article

(This article belongs to the Special Issue Complex Infectious Issues in Critically Ill Patients)

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13 pages, 1467 KiB

Open AccessReview

Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

by Claire Roger and Benjamin Louart

Microorganisms 2021, 9(7), 1505; https://doi.org/10.3390/microorganisms9071505 - 14 Jul 2021

Cited by 53 | Viewed by 9002

Abstract

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk [...] Read more.

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals. Full article

(This article belongs to the Special Issue Complex Infectious Issues in Critically Ill Patients)

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27 pages, 1217 KiB

Open AccessReview

Optimizing Antimicrobial Drug Dosing in Critically Ill Patients

by Pedro Póvoa, Patrícia Moniz, João Gonçalves Pereira and Luís Coelho

Microorganisms 2021, 9(7), 1401; https://doi.org/10.3390/microorganisms9071401 - 28 Jun 2021

Cited by 27 | Viewed by 10463

Abstract

A fundamental step in the successful management of sepsis and septic shock is early empiric antimicrobial therapy. However, for this to be effective, several decisions must be addressed simultaneously: (1) antimicrobial choices should be adequate, covering the most probable pathogens; (2) they should [...] Read more.

A fundamental step in the successful management of sepsis and septic shock is early empiric antimicrobial therapy. However, for this to be effective, several decisions must be addressed simultaneously: (1) antimicrobial choices should be adequate, covering the most probable pathogens; (2) they should be administered in the appropriate dose, (3) by the correct route, and (4) using the correct mode of administration to achieve successful concentration at the infection site. In critically ill patients, antimicrobial dosing is a common challenge and a frequent source of errors, since these patients present deranged pharmacokinetics, namely increased volume of distribution and altered drug clearance, which either increased or decreased. Moreover, the clinical condition of these patients changes markedly over time, either improving or deteriorating. The consequent impact on drug pharmacokinetics further complicates the selection of correct drug schedules and dosing during the course of therapy. In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. We aim to review the available literature to assess the challenges, impact, and tools to optimize individualization of antimicrobial dosing to maximize exposure and effectiveness in critically ill patients. Full article

(This article belongs to the Special Issue Complex Infectious Issues in Critically Ill Patients)

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39 pages, 1880 KiB

Open AccessReview

Nosocomial Pneumonia in the Era of Multidrug-Resistance: Updates in Diagnosis and Management

by Elena Xu, David Pérez-Torres, Paraskevi C. Fragkou, Jean-Ralph Zahar and Despoina Koulenti

Microorganisms 2021, 9(3), 534; https://doi.org/10.3390/microorganisms9030534 - 5 Mar 2021

Cited by 16 | Viewed by 5674

Abstract

Nosocomial pneumonia (NP), including hospital-acquired pneumonia in non-intubated patients and ventilator-associated pneumonia, is one of the most frequent hospital-acquired infections, especially in the intensive care unit. NP has a significant impact on morbidity, mortality and health care costs, especially when the implicated pathogens [...] Read more.

Nosocomial pneumonia (NP), including hospital-acquired pneumonia in non-intubated patients and ventilator-associated pneumonia, is one of the most frequent hospital-acquired infections, especially in the intensive care unit. NP has a significant impact on morbidity, mortality and health care costs, especially when the implicated pathogens are multidrug-resistant ones. This narrative review aims to critically review what is new in the field of NP, specifically, diagnosis and antibiotic treatment. Regarding novel imaging modalities, the current role of lung ultrasound and low radiation computed tomography are discussed, while regarding etiological diagnosis, recent developments in rapid microbiological confirmation, such as syndromic rapid multiplex Polymerase Chain Reaction panels are presented and compared with conventional cultures. Additionally, the volatile compounds/electronic nose, a promising diagnostic tool for the future is briefly presented. With respect to NP management, antibiotics approved for the indication of NP during the last decade are discussed, namely, ceftobiprole medocaril, telavancin, ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. Full article

(This article belongs to the Special Issue Complex Infectious Issues in Critically Ill Patients)

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