Pharmacotherapies for multidrug-resistant gram-positive infections: current options and beyond.

INTRODUCTION: Infections due to multidrug-resistant organisms (MDRO) are a serious concern for public health with high morbidity and mortality. Though many antibiotics have been introduced to manage these infections, there are remaining concerns regarding the optimal management of Gram-positive MDROs. AREAS COVERED: A literature search on the PubMed/Medline database was conducted. We applied no language and time limits for the search strategy. In this narrative review, we discuss the current options for managing Gram-positive MDROs as well as non-traditional antibacterial agents in development. EXPERT OPINION: Despite their introduction more than 70 years ago, glycopeptides are still the cornerstone in treating Gram-positive infections: all registrative studies of new antibiotics have glycopeptides as control; these studies are designed as not inferior studies, therefore it is almost impossible to give recommendations other than the use of glycopeptides in the treatment of Gram-positive infections. The best evidence on treatments different from glycopeptides comes from post-hoc analysis and meta-analysis. Non-traditional antibacterial agents are being studied to aid in short and effective antibiotic therapies. The use of non-traditional antibacterial agents is not restricted to replacing traditional antibacterial agents with alternative therapies; instead, they should be used in combination with antibiotic therapies.

Medicinal cannabis products for the treatment of acute pain.

For thousands of years, medicinal cannabis has been used for pain treatment, but its use for pain management is still controversial. Meta-analysis of the literature has shown contrasting results on the addition of cannabinoids to opioids compared with placebo/other active agents to reduce pain. Clinical studies are mainly focused on medicinal cannabis use in chronic pain management, for which the analgesic effect has been proven in many studies. This review focuses on the potential use of medical cannabis for acute pain management in preclinical studies, studies on healthy subjects and the few pioneering studies in the clinical setting.

Antimicrobial approach of abdominal post-surgical infections.

Abdominal surgical site infections (SSIs) are infections that occur after abdominal surgery. They can be superficial, involving the skin tissue only, or more profound, involving deeper skin tissues including organs and implanted materials. Currently, SSIs are large global health problem with an incidence that varies significantly depending on the United Nations' Human Development Index. The purpose of this review is to provide a practical update on the latest available literature on SSIs, focusing on causative pathogens and treatment with an overview of the ongoing studies of new therapeutic strategies.

Plazomicin against Multidrug-Resistant Bacteria: A Scoping Review.

Plazomicin is a next-generation semisynthetic aminoglycoside antibiotic that can be used to treat infections by multi-resistant bacteria. It is effective against many bacteria-producing carbapenemases or other specific hydrolases. This scoping review aims to define the role acquired by plazomicin from its approval by the FDA (US Food and Drug Administration) in 2018 to the present day. Furthermore, we aim to provide a base for a future meta-analysis. This project was conducted following the recommendations presented in the PRISMA extension for scoping reviews and the JBI Manual for Evidence Synthesis. Among 901 potentially engaging citations, 345 duplicates were removed, and only 81 articles were selected for the analysis. According to the data analysis, plazomicin has been used to treat urinary tract infections, bloodstream infections, and ventilation-associated pneumonia. The pathogens killed included multi-resistant E. coli, K. pneumoniae, A. baumannii, P. aeruginosa, and S. aureus. Plazomicin can be a manageable, valid non-beta-lactam alternative for treating multi-resistant bacteria infections.

A Literature Overview of Secondary Peritonitis Due to Carbapenem-Resistant Enterobacterales (CRE) in Intensive Care Unit (ICU) Patients.

This comprehensive review of the recently published literature offers an overview of a very topical and complex healthcare problem: secondary peritonitis from multidrug-resistant pathogens, especially carbapenem-resistant Enterobacterales (CRE). Spontaneous secondary peritonitis and postsurgical secondary peritonitis are among the major causes of community- and healthcare- acquired sepsis, respectively. A large number of patients enter ICUs with a diagnosis of secondary peritonitis, and a high number of them reveal infection by CRE, P. aeruginosa or A. baumannii. For this reason, we conceived the idea to create a synthetic report on this topic including updated epidemiology data, a description of CRE resistance patterns, current strategies of antimicrobial treatment, and future perspectives. From this update it is clear that antimicrobial stewardship and precision medicine are becoming essential to fight the emergence of antimicrobial resistance and that even if there are new drugs effective against CRE causing secondary peritonitis, these drugs have to be used carefully especially in empirical therapy.

Opioid sparing effect of intravenous dexmedetomidine in orthopaedic surgery: a retrospective analysis.

BACKGROUND: Dexmedetomidine is a highly selective alpha-2 receptor agonist without any effect on the GABA receptor. It provides an excellent sedative and analgesic profile with few side effects. We report our experience with dexmedetomidine use during orthopaedic surgery under locoregional anaesthesia to ensure adequate sedation and optimal postoperative pain control. METHODS: In this retrospective analysis, we included 128 patients who underwent orthopaedic surgery between January 2019 and December 2021. All patients received the same local anaesthetic dose of 20 ml of ropivacaine 0.375% + mepivacaine 0.5% for axillary and supraclavicular block and 35 ml of ropivacaine 0.375% + mepivacaine 0.5% for triple nerve block (femoral, obturator and sciatic nerve). The cohort was divided into two groups based on sedation drugs used during surgery (dexmedetomidine, or group D, vs midazolam, or group M). All patients received postoperative 24-h analgesia consisting of 60 mg of ketorolac, 200 mg of tramadol and 4 mg of ondansetron. The primary outcome measured how many patients in the two groups required an analgesic rescue dose of pethidine and the time to first pethidine administration. To reduce confounding, we included patients in two groups with non-statistically different demo-anamnestic parameters and who received the same dose of intraoperative local anaesthetic and postoperative analgesia. RESULTS: The number of patients in group D who did not require a rescue dose of analgesia was significantly greater than in group M (49 vs 11, p < 0.001). Time-to-first postoperative opioid administration did not show a fundamental difference between the two groups under examination (523.75 ± 131.55 min vs 564 ± 117.84 min). Total opioid consumption was higher in the M group than in the D group (3529.8 ± 30.36 µg vs 1864.8 ± 31.59 µg, p 0.075), with a mean opioid consumption significantly higher in the M group than in the D group (26.26 ± 42.8 µg vs 69.21 ± 46.1 µg, p < 0.001): D group received 62.06% less opioid than M group. CONCLUSIONS: The continuous infusion of dexmedetomidine during orthopaedic surgery performed under locoregional anaesthesia has been shown to increase the analgesic effect of local anaesthetics and reduce the consumption of major opioids in the postoperative period. Dexmedetomidine offers a unique ability to supply sedation and analgesia without respiratory depression, having a wide safety margin and an excellent sedative capacity. It does not increase the rate of postoperative complications.

Blood Stream Infections from MDR Bacteria.

BACKGROUND: Bloodstream infections (BSIs) constitute a growing public health concern, are among the most severe nosocomial pathologies, and are considered a worldwide cause of unfaithful outcomes, increasing treatment costs and diagnostic uncertainties. BSIs are one of the most frequent lethal conditions that are managed in intensive care units (ICUs). In the case of septic shock, immune deficiency, and delayed treatment, even with adequate antimicrobial therapy and/or source control, the outcomes are often unfavorable. METHODS: this review article summarizes the epidemiological and microbiological characteristics of BSIs with a particular focus on ICU acquired BSIs (ICU-BSIs), which are usually caused by multidrug-resistant (MDR) pathogens. For this reason, their antimicrobial resistance patterns and therapeutic options have also been compiled. RESULTS: ICU-acquired BSIs prevail in 5-7% of ICU patients. Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosae are the pathogens most often responsible for MDR infections. MDR Enterobacteriaceae have seen their prevalence increase from 6.2% (1997-2000) to 15.8% (2013-2016) in recent years. CONCLUSIONS: Considering that prevention and treatment of sepsis is nowadays considered a global health priority by the World Health Organization, it is our obligation to invest more resources into solving or reducing the spread of these unfaithful infections. It is relevant to identify patients with risk factors that make them more susceptible to BSIs, to guarantee earlier molecular or microbiological diagnoses, and more rapidly appropriate treatment by using de-escalation strategies where possible.

A scoping review of retracted publications in anesthesiology.

CONTEXT: Fraudulent publication is a scourge of scientific research. OBJECTIVES: This scoping review was aimed at characterizing retracted publications for fraud or plagiarism in the field of anesthesia. Does the reputation of the journal (Quartile and Impact Factor, IF) protect the reader from the risk of having the manuscript he read withdrawn for fraud/plagiarism? METHODS/DESIGN: This scoping review was planned following the Joanna Briggs Institute recommendations. Data sources: PubMed and the Retraction Watch Database (http://retractiondatabase.org/RetractionSearch.aspx?). Study selection: All types of publications retracted. Data extraction: Year, first author nationality, journal name, journal category, IF, Quartile, H index. Data analysis: The association with Quartile and IF was investigated. RESULTS: No significant association between retraction of papers published in no-Quartile journals and retractions published in journals placed in the highest quartile. CONCLUSIONS: The quality of the surveillance in paper submission is not higher in journals of the first Quartile than in journals not placed in other Quartiles. (The protocol was prospectively registered in the Open Science Framework https://doi.org/10.17605/OSF.IO/TGKNE).

Ceftolozane-Tazobactam Combination Therapy Compared to Ceftolozane-Tazobactam Monotherapy for the Treatment of Severe Infections: A Systematic Review and Meta-Analysis.

Ceftolozane-tazobactam (C/T) is a combination of an advanced-generation cephalosporin (ceftolozane) with a ß-lactamase inhibitor (tazobactam). It is approved for the treatment of complicated urinary-tract/intra-abdominal infections and hospital-acquired/ventilator-associated pneumonia. This systematic review and meta-analysis (registered prospectively on PROSPERO, no. CRD42019134099, on 20 January 2020) aimed to evaluate the effectiveness of C/T combination therapy compared to C/T monotherapy for the treatment of severe infections and to describe the prevalence of microorganisms in the included studies. We retrieved literature from PubMed, EMBASE, and CENTRAL, until 26 November 2020. Eligible studies were both randomised trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was all-cause mortality; secondary outcomes were (i) clinical improvement and (ii) microbiological cure. Eight nonrandomised studies were included in the qualitative synthesis: Seven retrospective cohort studies and one case-control study. The meta-analysis of the four studies evaluating all-cause mortality (in total 148 patients: 87 patients treated with C/T alone and 61 patients treated with C/T combination therapy) showed a significant reduction of mortality in patients receiving C/T combination therapy, OR: 0.31, 95% CI: 0.10-0.97, p = 0.045. Conversely, the meta-analysis of the studies evaluating clinical improvement and microbiological cure showed no differences in C/T combination therapy compared to C/T monotherapy. The most consistent data come from the analysis of the clinical improvement, n = 391 patients, OR: 0.97, 95% CI: 0.54-1.74, p = 0.909. In 238 of the 391 patients included (60.8%), C/T was used for the treatment of infections caused by Pseudomonas aeruginosa.

Current status of COVID-19 treatment: An opinion review.

The pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has garnered the attention of scientists worldwide in the search for an effective treatment while also focusing on vaccine development. Several drugs have been used for the management of coronavirus disease 2019 (COVID-19), which has affected many hospitals and health centers worldwide. Statistically significant results are lacking on the effectiveness of the experimented drugs in reducing COVID-19 morbidity or mortality, as there are very few published randomized clinical trials. Despite this, the literature offers some material for study and reflection. This opinion review attempts to address three burning questions on COVID-19 treatment options. (1) What kind of studies are currently published or ongoing in the treatment of patients with COVID-19? (2) What drugs are currently described in the literature as options of treatment for patients affected by the infection? And (3) Are there specific clinical manifestations related to COVID-19 that can be treated with a customized and targeted therapy? By answering these questions, we wish to create a summary of current COVID-19 treatments and the anti-COVID-19 treatments proposed in the recent clinical trials developed in the last 3 mo, and to describe examples of clinical manifestations of the SARS-CoV-2 infection with a cause-related treatment.

Local infiltration of tramadol as an effective strategy to reduce post-operative pain: a systematic review protocol and meta-analysis.

OBJECTIVE: The purpose of this review is to evaluate the use and effectiveness of the local administration of tramadol in reducing post-operative pain during surgical interventions. METHODS: The PubMed, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases will be searched for this review. This systematic review will include studies evaluating the clinical efficacy of the local infiltration of tramadol, with no study design restrictions. Only studies that present clear descriptions of local tramadol administration are published in peer-reviewed journals in the English, Italian, Spanish, French, Portuguese or German language and are published in full will be taken into consideration. A meta-analysis will be performed when there is sufficient clinical homogeneity among the retrieved studies, and only randomized controlled studies and quasi-randomized controlled studies will be included. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess the certainty in the evidence. If a quantitative analysis cannot be conducted, a qualitative description of the results of the retrieved studies will be provided. RESULTS: A high-quality synthesis of the current evidence on the local administration of tramadol for managing post-surgical pain will be illustrated using subjective reports and objective measures of performance. The primary outcomes will include the magnitude of post-operative pain intensity improvement, with improvement being as defined by a reduction by at least 2 points in the visual analogue scale (VAS) score or numerical rating scale (NRS) score. The secondary outcomes will be the magnitude of reduction in tramadol rescue doses and in other analgesic drug doses. CONCLUSION: This protocol will present evidence on the efficacy of tramadol in relieving post-surgical pain. SYSTEMIC REVIEW REGISTRATION: PROSPERO CRD42018087381.

Ceftazidime-Avibactam Combination Therapy Compared to Ceftazidime-Avibactam Monotherapy for the Treatment of Severe Infections Due to Carbapenem-Resistant Pathogens: A Systematic Review and Network Meta-Analysis.

Ceftazidime-avibactam (CZA) is a novel beta-lactam beta-lactamase inhibitor combination approved for the treatment of complicated urinary tract infections, complicated intra-abdominal infections, and for hospital-acquired/ventilator-associated pneumonia. The aim of this systematic review (PROSPERO registration number: CRD42019128927) was to evaluate the effectiveness of CZA combination therapy versus CZA monotherapy in the treatment of severe infections. The databases included in the search, until February 12th, 2020, were MEDLINE by PubMed, EMBASE, and The Cochrane Central Register of Controlled Trials. We included both randomized controlled trials (RCTs) and non-randomized studies published in peer-reviewed journals and in the English language. The primary outcome was all-cause mortality (longest follow-up) evaluated in patients with the diagnosis of infection with at least one pathogen; secondary outcomes were clinical and microbiological improvement/cure. Thirteen studies were included in the qualitative synthesis: 7 RCTs and 6 retrospective studies All the six retrospective studies identified carbapenamase-producing Enterobacteriaceae (CRE) as the cause of infection and for this reason were included in the network meta-analysis (NMA); the quality of the studies, assessed using the New Castle-Ottawa Scale, was moderate-high. In all the six retrospective studies included in the NMA, CZA was used in large part for off-label indications (mostly blood stream infections: 80-100% of patients included). No difference in mortality rate was observed in patients undergoing CZA combination therapy compared to CZA monotherapy [n = 503 patients, direct evidence OR: 0.96, 95% CI: 0.65-1.41].

Gut microbiota and nutrient interactions with skin in psoriasis: A comprehensive review of animal and human studies.

The intestinal tract (i.e., the gut), is where the body's nutrients are absorbed, and is simultaneously inhabited by numerous microbes. An increasing body of literature suggests a crucial role for the gut microbiome in modulating systemic inflammatory disease. Psoriasis is a chronic systemic inflammatory disease and its pathogenesis is related to the interaction between genetic susceptibility, immune response and environmental triggers. The omics era has allowed physicians to assess different aspects of psoriasis pathogenesis such as the microbiome, infectome, and autoinfectome. Furthermore, diet appears to play an important role in modulating disease activity, perhaps by influencing gut microbes. Given these observations, we aimed to summarize the current knowledge regarding skin-microbiome-gut-nutrients and psoriasis.

Antimicrobial Lock Therapy in Clinical Practice: A Scoping Review Protocol.

Our objective is to review the scientific literature on the use of antimicrobial lock therapy (ALT). To achieve this result, our scoping review will address the following seven key questions: 1) Who are the patients who will benefit from this technique? 2) What are the techniques utilized? 3) What are the settings in which the technique is performed? 4) When the technique is performed? 5) Why the technique is performed? 6) How the technique is performed? 7) In how much amount, of such technique performed? This review considers all studies published in full and in peer-reviewed journals, with no restrictions on language, on the year of publication and age of the participants. Both randomized controlled trials and observational studies will be included. This scoping review has been planned on a five-stage framework: 1. Identifying the review question; 2. identifying relevant studies; 3. study selection; 4. charting the data; 5. collating, summarizing, and reporting the results. It is conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. The databases utilized will include MEDLINE via PubMed, EMBASE and Cochrane Central Register of Controlled Trials and Grey Literature. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/vphwm/.

Spontaneous bacterial peritonitis due to carbapenemase-producing Enterobacteriaceae: Etiology and antibiotic treatment.

Carbapenem antibiotics were first introduced in the 1980s and have long been considered the most active agents for the treatment of multidrug-resistant gram-negative bacteria. Over the last decade, carbapenem-resistant Enterobacteriaceae (CRE) have emerged as organisms causing spontaneous bacterial peritonitis. Infections caused by CRE have shown a higher mortality rate than those caused by bacteria sensitive to carbapenem antibiotics. Current antibiotic guidelines for the treatment of spontaneous bacterial peritonitis are insufficient, and rapid de-escalation of empiric antibiotic treatment is not widely recognized. This review summarizes the molecular characteristics, epidemiology and possible treatment of spontaneous bacterial peritonitis caused by CRE.

First Italian outbreak of VIM-producing Serratia marcescens in an adult polyvalent intensive care unit, August-October 2018: A case report and literature review.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae has become a significant public health concern as hospital outbreaks are now being frequently reported and these organisms are becoming difficult to treat with the available antibiotics. CASE SUMMARY: An outbreak of VIM-producing Serratia marcescens occurred over a period of 11 wk (August, 1 to October, 18) in patients admitted to the adult polyvalent intensive care unit of the University of Campania "Luigi Vanvitelli" located in Naples. Four episodes occurred in three patients (two patients infected, and one patient colonized). All the strains revealed the production of VIM. CONCLUSION: After three decades of carbapenem antibiotics use, the emergence of carbapenem-resistance in Enterobacteriaceae has become a significant concern and a stricter control to preserve its clinical application is mandatory. This is, to our knowledge, the first outbreak of VIM-producing Serratia marcescens in Europe. Surveillance policies must be implemented to avoid future outbreaks.

Dexmedetomidine as adjunctive therapy for the treatment of alcohol withdrawal syndrome: a systematic review protocol.

OBJECTIVE: The purpose of this review is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care (benzodiazepines) compared to either the standard of care or other adjunctive treatment approaches (e.g. benzodiazepines plus propofol) for the treatment of alcohol withdrawal syndrome (AWS). INTRODUCTION: Benzodiazepines have been the cornerstone of AWS therapy, but in some patients, AWS is refractory to high doses. Moreover, benzodiazepine use is burdened by excessive sedation, confusion and respiratory depression. Options for management of refractory AWS include the addition of phenobarbital, propofol and, more recently, dexmedetomidine to benzodiazepines therapy. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the intensive care unit. INCLUSION CRITERIA: This review will consider studies including patients who are 18 years or older and are diagnosed with AWS. The exclusion criteria are a history of psychoactive substances or withdrawal states and/or severe neurologic disorder (e.g. traumatic brain injury, acute stroke, severe dementia, seizure disorder). METHODS: This review will include only studies published in English, with no restrictions on the year of publication. Both randomized controlled trials and observational studies (including cohort and case-control studies) assessing the drug effectiveness and safety will be included. The databases utilized will include: PubMed, Embase and Cochrane Central Register of Controlled Trials. In addition, the trial registers to be searched will include: World Health Organization International Clinical Trials Registry Platform (ICTRP), U.S. National Library of Medicine Drug Information Portal and ClinicalTrials.gov. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42018084370.

Spontaneous bacterial peritonitis caused by Gram-negative bacteria: an update of epidemiology and antimicrobial treatments.

Introduction: Spontaneous bacterial peritonitis (SBP) is a main infectious complication in end-stage liver disease (ESLD) patients. The increasing trend of bacterial resistance in ESLD patients with SBP has been associated with low treatment efficacy of traditional therapy. Cephalosporin use has been restricted to community-acquired infections and in areas/health care settings with low rates of multidrug-resistant (MDR) bacteria. To date, several changes are necessary with regard to empiric therapy recommendations in areas/health care settings with high rates of MDR bacteria. Areas covered: An overview of the epidemiology and antimicrobial treatments of SBP caused by Gram-negative bacteria. Expert opinion: Broad-spectrum antibiotics have been recommended as empiric therapy for suspected SBP in areas/health care settings with high rates of MDR bacteria and secondary treatment, with newer antibiotics, for SBP caused by MDR-Gram-negative bacteria (i.e. new beta-lactam/beta-lactamase inhibitor combinations, cefiderocol, plazomicin, and eravacycline) either alone or in combination.

New antimicrobial options for the management of complicated intra-abdominal infections.

Complicated intra-abdominal infections (cIAIs) are a common cause of morbidity and mortality in surgical patients. Optimal management of cIAI requires early source control in combination with adequate antimicrobial treatment and aggressive fluid resuscitation. cIAIs are mainly caused by Gram-negative bacilli and anaerobes. Broad-spectrum single-agent or combination drug regimens against these microorganisms are the mainstay of therapy. However, development of antimicrobial resistance has become an increasingly large concern: multidrug-resistant organisms are associated with a higher rate of inadequate antimicrobial therapy, which in turn is associated with higher mortality rate, longer hospital stay, and increased cost compared to adequate antimicrobial therapy. In this mini-review, we discuss the effectiveness of several new antimicrobial agents, recently approved or in advanced phases of clinical development, for the treatment of cIAIs, including the new beta-lactam and beta-lactamase inhibitor combinations (ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/cilastatin/relebactam, aztreonam/avibactam), siderophore cephalosporins (cefiderocol), aminoglycosides (plazomicin), and tetracyclines (eravacycline).

Clinical applications of palmitoylethanolamide in pain management: protocol for a scoping review.

BACKGROUND: Palmitoylethanolamide (PEA) belong to endocannabinoid family, a group of fatty acid amides. PEA has been proven to have analgesic and anti-inflammatory activity and has been used in several controlled studies focused on the management of chronic pain among adult patients with different underlying clinical conditions. METHODS/DESIGN: A literature search will be performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The population will be patients who have chronic pain, the intervention will be the administration of PEA alone or in combination with other drugs for the pain management; the comparison will be the standard therapy in accordance with the current guidelines for the treatment of pain. The Outcomes will be the reduction of pain not restricted to specific scales laying out the pain outcome data described in the included studies. DISCUSSION: This scoping review aims to describe the clinical applications of the PEA in chronic pain management and its outcome. SCOPING REVIEW REGISTRATION: Open Science Framework https://osf.io/74tmx/ .