Food-induced methemoglobinemia: A systematic review.

Methemoglobinemia is a sporadic, potentially fatal disease of poor tissue oxygenation in which ferrous hemoglobin (Fe2+ ) is oxidized to the ferric (Fe3+ ) state, rendering it incapable of binding oxygen (O2 ). Fortunately, it is diagnosable and treatable. Here, we present a systematic review of food-induced methemoglobinemia. PubMed and Embase databases were searched using the term "methemoglobin*," for articles up to December 31, 2020. Inclusion criteria were confirmed or probable cases of methemoglobinemia with an oxidant confirmed in food or body tissue samples, or the oxidant likely to have come from food. We found 97 articles describing 568 cases. Median age was 6 years (range: 2 weeks to 80 years). Median methemoglobin fraction was 30% (n = 142). Oxidizing agents were predominantly nitrites and nitrates. The commonest type of presentation was children eating vegetables (30%), followed by accidental ingestions (27%), and meat curing misadventures (22%). Favism was found to result in mild methemoglobinemia, highest fraction reported was 15.8%. Of the 35 deaths, 32 were from accidental ingestions (91%). In some fatal cases, diagnosis was likely delayed or missed, and antidote was not administered. The majority of cases survived, even with severe methemoglobin levels of up to 89%, provided that methylene blue was administered. Treatment with methylene blue alone resulted in an average methemoglobin drop of 39.1% (n = 22). Methemoglobinemia cases continue to occur due to accidental exposure, meat curing misadventures, and babies ingesting nitrate-rich vegetables which have been inappropriately stored. Early recognition of the toxidrome, instituting antidote treatment, and notifying public health authorities are key to improved outcomes.

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

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.

Evaluation of the quality of evidence supporting guideline recommendations for the nutritional management of critically ill adults.

AIMS: The primary aim of this study was to evaluate the quality of evidence supporting the 2019 European Society for Clinical Nutrition and Metabolism (ESPEN) and 2016 American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations for medical nutrition therapy in critically ill patients. Secondary objectives are to assess the differences between 2019 ESPEN and 2016 ASPEN recommendations and to inform relevant stakeholders of areas requiring improvement in the research. METHODS: The 2019 ESPEN and 2016 ASPEN guidelines were identified and downloaded from the official websites. The level of evidence and strength of recommendations from the guidelines were standardised to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Level of evidence was classified as high-quality (randomised controlled trials (RCTs) without important limitations), moderate-quality (downgraded RCTs or upgraded observational studies) or low-quality (observational studies without specific strengths or important limitations, case series, case reports). In addition, good practice points (GPP; recommendations based on the clinical experience of the guideline development group) were considered. Strength of recommendation was reported as strong or weak. RESULTS: From 152 total recommendations, only five (3.3%) were supported by high-quality evidence, with 14 being strong recommendations. A total of 79 (52.0%) recommendations were GPPs. Overall, the proportion of recommendations supported by high-quality (7% [ESPEN] vs. 1.1% [ASPEN], p < 0.05) and moderate-quality evidence (33.3% [ESPEN] vs. 8.4% [ASPEN], p < 0.01) was significantly higher in ESPEN guidelines. On the other hand, ASPEN guidelines reported a greater proportion of recommendations supported by GPPs (58.9% [ASPEN] vs. 40.4% [ESPEN], p = 0.03). In enteral and parenteral nutrition, the proportion of recommendations supported by moderate-quality evidence (50% [ESPEN] vs. 15.8% [ASPEN], p < 0.01) was significantly higher in ESPEN guidelines. CONCLUSION: Published guideline recommendations for the nutritional management of critically ill adults remain largely supported by expert opinion and only a minority by high-quality evidence. An urgent unmet clinical need for high-quality clinical trials is warranted.

Quality of evidence supporting Surviving Sepsis Campaign Recommendations.

INTRODUCTION: The Surviving Sepsis Campaign (SSC) guidelines, released in 2017, are a combination of expert opinion and evidence-based medicine, adopted by many institutions as a standard of practice. The aim was to analyse the quality of evidence supporting recommendations on the management of sepsis. METHODS: The strength and quality of evidence (high, moderate, low-very low and best practice statements) of each recommendation were extracted. Randomised controlled trials were required to qualify as high-quality evidence. RESULTS: A total of 96 recommendations were formulated, and 87 were included. Among thirty-one (43%) strong recommendations, only 15.2% were supported by high-quality evidence. Overall, thirty-seven (42.5%) recommendations were based on low-quality evidence, followed by 28 (32.2%) based on moderate-quality, 15 (17.2%) were best practice statements and only seven (8.0%) were supported by high-quality evidence. Randomised controlled trials supported 21.4%, 9.5% and 8.6% recommendations on mechanical ventilation, resuscitation, and management/adjuvant therapy, respectively. In contrast, none high-quality evidence recommendation supported antimicrobial/source control (82.4% were low-very low evidence or best practice statements), and nutrition. CONCLUSIONS: In the SSC guidelines most recommendations were informed by indirect evidence and non-systematic observations. While awaiting trials results, Delphi-like approaches or multi-criteria decision analyses should guide recommendations.

Ventilator-Associated Tracheobronchitis: To Treat or Not to Treat?

Ventilator-associated tracheobronchitis (VAT) is an infection commonly affecting mechanically ventilated intubated patients. Several studies suggest that VAT is associated with increased duration of mechanical ventilation (MV) and length of intensive care unit (ICU) stay, and a presumptive increase in healthcare costs. Uncertainties remain, however, regarding the cost/benefit balance of VAT treatment. The aim of this narrative review is to discuss the two fundamental and inter-related dilemmas regarding VAT, i.e., (i) how to diagnose VAT? and (ii) should we treat VAT? If yes, should we treat all cases or only selected ones? How should we treat in terms of antibiotic choice, route, treatment duration?

Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms.

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

Lefamulin. Comment on: "Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms. Microorganisms, 2019, 7, 270".

On 18 August 2019, an article was published in Microorganisms presenting novel, approved anti-Gram-positive antibiotics. On 19 August 2019, the U.S. Food and Drug Administration announced the approval of lefamulin, a representative of a new class of antibiotics, the pleuromutilins, for the treatment of adult community-acquired bacterial pneumonia. We present a brief description of lefamulin.

Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms.

Increasing multidrug-resistance to Gram-positive pathogens, particularly to staphylococci, enterococci and streptococci, is a major problem, resulting in significant morbidity, mortality and healthcare costs. In recent years, only a small number of novel antibiotics effective against Gram-positive bacteria has been approved. This review will discuss the current evidence for novel branded antibiotics that are highly effective in the treatment of multidrug-resistant infections by Gram-positive pathogens, namely ceftobiprole, ceftaroline, telavancin, oritavancin, dalbavancin, tedizolid, besifloxacin, delafloxacin, ozenoxacin, and omadacycline. The mechanism of action, pharmacokinetics, microbiological spectrum, efficacy and safety profile will be concisely presented. As for any emerging antibiotic agent, resistance is likely to develop against these highly effective antibiotics. Only through appropriate dosing, utilization and careful resistance development monitoring will these novel antibiotics continue to treat Gram-positive pathogens in the future.

Correction to: The relationship between ventilator-associated pneumonia and chronic obstructive pulmonary disease: What is the current evidence?

Unfortunately, the Acknowledgements section was not included in the original version of the article. The said section is given here.

The relationship between ventilator-associated pneumonia and chronic obstructive pulmonary disease: what is the current evidence?

Chronic obstructive pulmonary disease (COPD) affects approximately 65 million people from which > 25% will require intensive care unit (ICU) admission. Ventilator-associated pneumonia (VAP) is the commonest ICU infection and results in increased morbidity/mortality and costs. The literature on the interaction between COPD and VAP is scarce and controversial. The project aimed to search the literature in order to address the following: (i) Is COPD a risk factor for VAP development? (ii) Does COPD impact the outcome of patients with VAP? (iii) Does VAP development impact the outcome of COPD patients? (iv) Does COPD impact the aetiology of VAP? Current evidence on the topic is controversial. Regarding the impact of VAP on COPD patients, the majority of the existing limited number of studies suggests that VAP development results in higher mortality and longer duration of mechanical ventilation and ICU stay. Also, the majority of the studies exploring the impact of COPD on VAP outcomes suggest that COPD is independently associated with a decrease in survival, although the number of such studies is limited. Regarding the aetiology, Pseudomonas aeruginosa is the most frequent pathogen in VAP patients with COPD. Noteworthy, one study suggests that P. aeruginosa is higher in COPD patients even in the early-onset VAP subgroup. This manuscript provides a comprehensive overview of the available literature on the interaction between COPD and VAP, highlighting the differences and limitations that may have led to controversial results, and it may act as a platform for further research with important clinical implications.