Marios Karvouniaris - Academia.edu (original) (raw)

Papers by Marios Karvouniaris

Antibiotics

Gram-negative bacterial resistance to antimicrobials has had an exponential increase at a global ... more Gram-negative bacterial resistance to antimicrobials has had an exponential increase at a global level during the last decades and represent an everyday challenge, especially for the hospital practice of our era. Concerted efforts from the researchers and the industry have recently provided several novel promising antimicrobials, resilient to various bacterial resistance mechanisms. There are new antimicrobials that became commercially available during the last five years, namely, cefiderocol, imipenem-cilastatin-relebactam, eravacycline, omadacycline, and plazomicin. Furthermore, other agents are in advanced development, having reached phase 3 clinical trials, namely, aztreonam-avibactam, cefepime-enmetazobactam, cefepime-taniborbactam, cefepime-zidebactam, sulopenem, tebipenem, and benapenem. In this present review, we critically discuss the characteristics of the above-mentioned antimicrobials, their pharmacokinetic/pharmacodynamic properties and the current clinical data.

World Journal of Clinical Cases, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to glo... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global public health. The virus causes the clinical syndrome known as coronavirus disease 2019 (COVID-19), in which multiple organs can get affected. Apart from manifestations of the respiratory system, which predominate, its clinical presentation is frequently accompanied by symptoms of the gastro-intestinal (GI) tract and liver abnormalities. The correlation of symptoms and abnormalities with disease severity is discussed, leading to ambiguous results from international literature. Moreover, the disease infects patients with co-existing liver and GI disorders affecting both their health status and the availability of healthcare services provided to them. The risk of transmission of the disease during aerosol-generating procedures has changed the diagnostic approach and follow-up algorithms for liver and GI diseases. For the safety of both doctors and patients, telemedicine and distant evaluation have become everyday practice, whereas several routines and emergency visits at outpatient and emergency departments have been postponed or delayed. Vaccination against SARS-CoV-2 is underway, providing hope to humanity and the expectation that the post-COVID-19 era is near. This review aims to update knowledge about the manifestations of COVID-19 related to liver and GI diseases and the effect of the pandemic on the diagnostic and therapeutic procedures for these diseases with a special focus on how current practices have changed and what changes will possibly remain in the future.

Reviews on Recent Clinical Trials, 2011

MRSA infections, especially pneumonia have been associated with considerable morbidity and mortal... more MRSA infections, especially pneumonia have been associated with considerable morbidity and mortality and the management of MRSA infections is considered as an issue of high priority for scientific societies. Many studies which have been published during the last 10 years have provided evidence for MRSA pneumonia epidemiology, diagnosis and treatment. The main regime of antibiotic treatment recommended for MRSA pneumonia is either vancomycin or linezolid. Despite its pK/pD superiority over vancomycin, linezolid has to date failed to show clear advantage over vancomycin in recent clinical trials.

Infectious Disorders - Drug Targets, 2011

Aim: To review available evidence for the role of adjunctive therapies in severe pneumonia. Metho... more Aim: To review available evidence for the role of adjunctive therapies in severe pneumonia. Methods: We focused on therapies that have attracted recently interest such as glucocorticosteroids (GCs), statins and recombinant activated protein-C. Results: Experimental animal and human studies showed that GCs are able to modulate the inflammatory response and may offer a benefit in patients with severe sepsis. Randomized trials in pneumonia are few, mostly limited in septic shock and ARDS patients. Recombinant activated protein C is a potent anticoagulant and profibrinolytic enzyme which can inhibit the systemic inflammatory response. Available data, although limited, showed that activated protein C can reduce mortality in severe sepsis, especially in severe pneumonia due to S. Pneumoniae. Statins have pleiotropic properties which can affect the inflammatory cascade. The use of statins has been found to be associated with decreased mortality in some studies with pneumina whereas the use of statins was associated with increased risk of death in others. However, data come from observational or retrospective studies. Conclusion: Treatment with GCs may modulate the inflammatory response in critically ill patients with pneumonia but a clear effect of steroids on survival is debatable. The administration of GCs should be considered in patients with severe pneumonia when vasopressor dependent septic shock. Activated protein-C may be considered in patients with severe CAP or HAP and sepsis or organ failure. The role of statins in the management of severe pneumonia remains controversial until data from clinical trails will be available.

We assessed if prophylactic nebulised colistin might reduce ventilator-associatedpneumonia (VAP) ... more We assessed if prophylactic nebulised colistin might reduce ventilator-associatedpneumonia (VAP) incidence in a setting, mixed medical-surgical ICU, where multidrug-resistant (MDR) bacteria were prevalent and endemic.We used a single-centre, two-arm, randomised, open-label, controlled trial in a 12-bed ICU in the University Hospital of Larissa, Greece. Patient inclusion criteria included mechanical ventilation of >48 h.The two arms consisted of prophylaxis with 500000 U colistin (Col group) or normal saline (NS group), thrice daily, for the first 10 ICU days or until extubation. The primary outcome of the study was the 30-day VAP incidence.In total, 168 patients entered the study. VAP incidence was not different between Col and NS group patients (14 (16.7%) versus 25 (29.8%), respectively, p=0.07). Regarding the secondary outcomes, the intervention resulted in a lower VAP incidence density rate (11.4 versus 25.6, respectively, p 48 ωρών. 168 ασθενείς έλαβαν μέρος στην παρούσα μη ...

Antibiotics, 2022

Intensive care unit patients may present infections by difficult-to-treat-resistant Gram-negative... 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...

Objective. Τo identify risk factors for the first episode of Klebsiella Pneumonia resistant to ca... more Objective. Τo identify risk factors for the first episode of Klebsiella Pneumonia resistant to carbapenems (KPRC) infection in critically ill patients. Design, Setting, and Methods. This prospective cohort study was conducted in a 12-bed general Intensive Care Unit (ICU) in a University Hospital on ICU patients who required mechanical ventilation (MV) for >48 hours during a 12-month period. Clinical and microbiologic data were studied. Characteristics of KPRC patients were compared with those of critically ill patients who presented nonmultidrug resistant (MDR) bacterial infections or no documented infection at all. Results. Twenty-five patients presented KPRC infection, 18 presented non-MDR bacterial infection, and 39 patients presented no infection. Compared to patients without documented infection or infected by nonMDR bacteria, patients with KPRC infection had received more frequently or for longer duration antibiotics against Gram-negative bacteria (carbapenems, colistin P &...

s of the 15th International Symposium on Infections in the Immunocompromised Host S41 acute pancr... more s of the 15th International Symposium on Infections in the Immunocompromised Host S41 acute pancreatitis (n=3). At study entry, 14 (74%) patients were in the ICU (median Simplified Acute Physiology Score II 45, range 31-65), 19 (100%) received antibacterial therapy and 17 (89%) were colonized with Candida (C. albicans in 69%; CCI ≥0.4 in 1/17 case, 5%). Median duration of CSP Px was 16 days (range 4-46). During CSP Px, 17 (89%) patients remained colonized (C. albicans in 68%), but 0/17 developed a CCI ≥0.4. CSP was successful for prevention of IC in 18 (95%) patients. Among 5 deaths, none was attributed to IC. No severe CSP-related SAE requiring discontinuation of Px occurred. Discussion: The results of this pilot study suggest that caspofungin is efficacious and safe for prophylaxis of intra-abdominal candidiasis in high-risk surgical patients. 98 Cultures of Venous Catheter Tips (VCT) from Intensive Care Unit Patients Stavroula Konstantopoulou, Athanasios Mourikis, Paraskevi Karle...

Expert Review of Anti-infective Therapy

ABSTRACT Introduction: Ventilator-associated pneumonia (VAP) is a common and potentially fatal co... more ABSTRACT Introduction: Ventilator-associated pneumonia (VAP) is a common and potentially fatal complication of mechanical ventilation that is often caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB). Despite the repurposing of older treatments and the novel antimicrobials, many resistance mechanisms cannot be confronted, and novel therapies are needed. Areas covered: We searched the literature for keywords regarding the treatment of GNB infections in mechanically ventilated patients. This narrative review presents new data on antibiotics and non-antibiotic approaches focusing on Phase 3 trials against clinically significant GNB that cause VAP. Expert opinion: Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam stand out as new options for infections by Klebsiella pneumoniae carbapenemase-producing bacteria, whereas ceftolozane-tazobactam adds therapeutic flexibility in Pseudomonas aeruginosa infections with multiple resistance mechanisms. Ceftazidime-avibactam and ceftolozane-tazobactam have relevant literature. Aztreonam-avibactam holds promise for the treatment of infections by metallo-β-lactamase (MBL)-producing organisms. Recently approved cefiderocol possesses an extended antibacterial spectrum, including KPC- and MBL-producers. However, recently published data have toned down optimism about treating VAP caused by carbapenem-resistant Acinetobacter baumannii. For the latter, eravacycline may provide additional hope, pending pertinent data. Non-antibiotic treatments currently being considered as adjunct therapeutic approaches are welcome. Nevertheless, they will hopefully substitute current antimicrobials in the future.

British journal of neurosurgery, 2021

Insertion of an external ventricular drain is a common procedure used in everyday practice by neu... more Insertion of an external ventricular drain is a common procedure used in everyday practice by neurosurgeons all around the world. It consists of the placement of an external ventricular drain (EVD) into the ventricular system providing the ability to measure intracranial pressure, and also divert the flow of cerebrospinal fluid (CSF) in a variety of pathological conditions. The most common complication is infection, and it may result in devastating consequences and negatively affect the outcome of these patients. The Infectious Diseases Society of America (IDSA), the Neurocritical Care Society (NCS), and The Society for Neuroscience in Anesthesiology & Critical Care (SNACC) have published recommendations for the management of EVD-Associated Ventriculitis. The objective of this study was to assess the methodological quality and reporting clarity of these recommendations using the AGREE-II tool. We found that the overall quality of the published clinical practice guidelines is accepta...

Expert Review of Anti-infective Therapy

Staphylococcus aureus is an important human pathogen that affects children worldwide. The number ... more Staphylococcus aureus is an important human pathogen that affects children worldwide. The number of publications discussing community-associated S. aureus infections, particularly in children, adolescents and young adults, has increased in recent years. This is related to the emergence and worldwide spread of community-associated methicillin-resistant S. aureus and the increase in severe life-threatening community-associated S. aureus infections. The increase in severity has been seen with both methicillin-resistant and methicillin-susceptible strains. This suggests that other virulence factors might be associated with the observed trend. Panton-Valentine leukocidin is a distinctive virulence factor associated with a highly aggressive and often fatal form of community-acquired infections. We propose that empiric treatment should be adapted to the type of infection and the resistance profile present in each country or region. In cases of severe infection, a combination of antibiotics, including at least one molecule active against protein synthesis such as clindamycin or linezolid, will be needed.

Cardiovascular Drugs and Therapy

Purpose Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We... more Purpose Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We sought to determine whether exposure to stress-dose steroids during and/or after cardiopulmonary resuscitation is associated with reduced risk of death due to postresuscitation septic shock. Methods We analyzed pooled, individual patient data from two prior, randomized clinical trials (RCTs). RCTs evaluated vasopressin, steroids, and epinephrine (VSE) during resuscitation and stress-dose steroids after resuscitation in vasopressorrequiring, in-hospital cardiac arrest. In the second RCT, 15 control group patients received open-label, stress-dose steroids. Patients with postresuscitation shock were assigned to a Steroids (n = 118) or No Steroids (n = 73) group according to an Bas-treated^principle. We used cumulative incidence competing risks Cox regression to determine cause-specific hazard ratios (CSHRs) for pre-specified predictors of lethal septic shock (primary outcome). In sensitivity analyses, data were analyzed according to the intention-to-treat (ITT) principle (VSE group, n = 103; control group, n = 88). Results Lethal septic shock was less likely in Steroids versus No Steroids group, CSHR, 0.40, 95% confidence interval (CI), 0.20-0.82; p = 0.012. ITT analysis yielded similar results: VSE versus Control, CSHR, 0.44, 95% CI, 0.23-0.87; p = 0.019. Adjustment for significant, between-group baseline differences in composite cardiac arrest causes such as Bhypotension and/or myocardial ischemia^did not appreciably affect the aforementioned CSHRs. Conclusions In this reanalysis, exposure to stress-dose steroids (primarily in the context of a combined VSE intervention) was associated with lower risk of postresuscitation lethal septic shock.

Journal of Intensive Care Medicine

Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdomina... more Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdominal hypertension (IAH). However, despite animal experimentation and physiological studies on humans in favor of this hypothesis, there is no definitive clinical data that IAH is associated with VAP. We therefore aimed to study whether IAH is a risk factor for increased incidence of VAP in critical care patients. This 1-center prospective observational cohort study was conducted in the intensive care unit of the University Hospital of Larissa, Greece, during 2013 to 2015. Consecutive patients were recruited if they presented risk factors for IAH at admission and were evaluated systematically for IAH and VAP for a 28-day period. Results: Forty-five (36.6%) of 123 patients presented IAH and 45 (36.6%) presented VAP; 24 patients presented VAP following IAH. Cox regression analysis showed that VAP was independently associated with IAH (1.06 [1.01-1.11]; P = .053), while there was an indication ...

Cardiovascular Drugs and Therapy

Journal of critical care, Jan 25, 2018

To test the potential of four common Toll-like receptor (TLR) polymorphisms to predispose to spec... more To test the potential of four common Toll-like receptor (TLR) polymorphisms to predispose to specific intensive care unit (ICU)-acquired infections and affect outcomes in a Greek ICU. The incidence of TLR2-Arg753Gln, TLR4-Asp299Gly, TLR4-Thr399Ile and TLR9-T1237C polymorphisms, and their association with ICU-acquired infections and patients' clinical outcomes were prospectively evaluated The examined genetic polymorphisms were assessed by real-time Polymerase-Chain-Reaction (PCR). During a 15-month period, 224 patients were enrolled and genotyped. The prevalence of genetic polymorphisms for TLR4-Asp299Gly, TLR4-Thr399Ile, mixed TLR4-Asp299Gly/Thr399Ile, TLR9-T1237C and TLR2-Arg753Gln was 14.4%, 14.7%, 11.2%, 24.5% and 2.2%, respectively. TLR4 polymorphisms were associated with increased susceptibility towards specific ICU-acquired infections, i.e. Gram-negative central-nervous-system infections (CNSI), ventilator-associated pneumonia (VAP) and urinary-tract infections (UTI), pri...

Antibiotics

Gram-negative bacterial resistance to antimicrobials has had an exponential increase at a global ... more Gram-negative bacterial resistance to antimicrobials has had an exponential increase at a global level during the last decades and represent an everyday challenge, especially for the hospital practice of our era. Concerted efforts from the researchers and the industry have recently provided several novel promising antimicrobials, resilient to various bacterial resistance mechanisms. There are new antimicrobials that became commercially available during the last five years, namely, cefiderocol, imipenem-cilastatin-relebactam, eravacycline, omadacycline, and plazomicin. Furthermore, other agents are in advanced development, having reached phase 3 clinical trials, namely, aztreonam-avibactam, cefepime-enmetazobactam, cefepime-taniborbactam, cefepime-zidebactam, sulopenem, tebipenem, and benapenem. In this present review, we critically discuss the characteristics of the above-mentioned antimicrobials, their pharmacokinetic/pharmacodynamic properties and the current clinical data.

World Journal of Clinical Cases, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to glo... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global public health. The virus causes the clinical syndrome known as coronavirus disease 2019 (COVID-19), in which multiple organs can get affected. Apart from manifestations of the respiratory system, which predominate, its clinical presentation is frequently accompanied by symptoms of the gastro-intestinal (GI) tract and liver abnormalities. The correlation of symptoms and abnormalities with disease severity is discussed, leading to ambiguous results from international literature. Moreover, the disease infects patients with co-existing liver and GI disorders affecting both their health status and the availability of healthcare services provided to them. The risk of transmission of the disease during aerosol-generating procedures has changed the diagnostic approach and follow-up algorithms for liver and GI diseases. For the safety of both doctors and patients, telemedicine and distant evaluation have become everyday practice, whereas several routines and emergency visits at outpatient and emergency departments have been postponed or delayed. Vaccination against SARS-CoV-2 is underway, providing hope to humanity and the expectation that the post-COVID-19 era is near. This review aims to update knowledge about the manifestations of COVID-19 related to liver and GI diseases and the effect of the pandemic on the diagnostic and therapeutic procedures for these diseases with a special focus on how current practices have changed and what changes will possibly remain in the future.

Reviews on Recent Clinical Trials, 2011

MRSA infections, especially pneumonia have been associated with considerable morbidity and mortal... more MRSA infections, especially pneumonia have been associated with considerable morbidity and mortality and the management of MRSA infections is considered as an issue of high priority for scientific societies. Many studies which have been published during the last 10 years have provided evidence for MRSA pneumonia epidemiology, diagnosis and treatment. The main regime of antibiotic treatment recommended for MRSA pneumonia is either vancomycin or linezolid. Despite its pK/pD superiority over vancomycin, linezolid has to date failed to show clear advantage over vancomycin in recent clinical trials.

Infectious Disorders - Drug Targets, 2011

Aim: To review available evidence for the role of adjunctive therapies in severe pneumonia. Metho... more Aim: To review available evidence for the role of adjunctive therapies in severe pneumonia. Methods: We focused on therapies that have attracted recently interest such as glucocorticosteroids (GCs), statins and recombinant activated protein-C. Results: Experimental animal and human studies showed that GCs are able to modulate the inflammatory response and may offer a benefit in patients with severe sepsis. Randomized trials in pneumonia are few, mostly limited in septic shock and ARDS patients. Recombinant activated protein C is a potent anticoagulant and profibrinolytic enzyme which can inhibit the systemic inflammatory response. Available data, although limited, showed that activated protein C can reduce mortality in severe sepsis, especially in severe pneumonia due to S. Pneumoniae. Statins have pleiotropic properties which can affect the inflammatory cascade. The use of statins has been found to be associated with decreased mortality in some studies with pneumina whereas the use of statins was associated with increased risk of death in others. However, data come from observational or retrospective studies. Conclusion: Treatment with GCs may modulate the inflammatory response in critically ill patients with pneumonia but a clear effect of steroids on survival is debatable. The administration of GCs should be considered in patients with severe pneumonia when vasopressor dependent septic shock. Activated protein-C may be considered in patients with severe CAP or HAP and sepsis or organ failure. The role of statins in the management of severe pneumonia remains controversial until data from clinical trails will be available.

We assessed if prophylactic nebulised colistin might reduce ventilator-associatedpneumonia (VAP) ... more We assessed if prophylactic nebulised colistin might reduce ventilator-associatedpneumonia (VAP) incidence in a setting, mixed medical-surgical ICU, where multidrug-resistant (MDR) bacteria were prevalent and endemic.We used a single-centre, two-arm, randomised, open-label, controlled trial in a 12-bed ICU in the University Hospital of Larissa, Greece. Patient inclusion criteria included mechanical ventilation of >48 h.The two arms consisted of prophylaxis with 500000 U colistin (Col group) or normal saline (NS group), thrice daily, for the first 10 ICU days or until extubation. The primary outcome of the study was the 30-day VAP incidence.In total, 168 patients entered the study. VAP incidence was not different between Col and NS group patients (14 (16.7%) versus 25 (29.8%), respectively, p=0.07). Regarding the secondary outcomes, the intervention resulted in a lower VAP incidence density rate (11.4 versus 25.6, respectively, p 48 ωρών. 168 ασθενείς έλαβαν μέρος στην παρούσα μη ...

Antibiotics, 2022

Intensive care unit patients may present infections by difficult-to-treat-resistant Gram-negative... 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...

Objective. Τo identify risk factors for the first episode of Klebsiella Pneumonia resistant to ca... more Objective. Τo identify risk factors for the first episode of Klebsiella Pneumonia resistant to carbapenems (KPRC) infection in critically ill patients. Design, Setting, and Methods. This prospective cohort study was conducted in a 12-bed general Intensive Care Unit (ICU) in a University Hospital on ICU patients who required mechanical ventilation (MV) for >48 hours during a 12-month period. Clinical and microbiologic data were studied. Characteristics of KPRC patients were compared with those of critically ill patients who presented nonmultidrug resistant (MDR) bacterial infections or no documented infection at all. Results. Twenty-five patients presented KPRC infection, 18 presented non-MDR bacterial infection, and 39 patients presented no infection. Compared to patients without documented infection or infected by nonMDR bacteria, patients with KPRC infection had received more frequently or for longer duration antibiotics against Gram-negative bacteria (carbapenems, colistin P &...

s of the 15th International Symposium on Infections in the Immunocompromised Host S41 acute pancr... more s of the 15th International Symposium on Infections in the Immunocompromised Host S41 acute pancreatitis (n=3). At study entry, 14 (74%) patients were in the ICU (median Simplified Acute Physiology Score II 45, range 31-65), 19 (100%) received antibacterial therapy and 17 (89%) were colonized with Candida (C. albicans in 69%; CCI ≥0.4 in 1/17 case, 5%). Median duration of CSP Px was 16 days (range 4-46). During CSP Px, 17 (89%) patients remained colonized (C. albicans in 68%), but 0/17 developed a CCI ≥0.4. CSP was successful for prevention of IC in 18 (95%) patients. Among 5 deaths, none was attributed to IC. No severe CSP-related SAE requiring discontinuation of Px occurred. Discussion: The results of this pilot study suggest that caspofungin is efficacious and safe for prophylaxis of intra-abdominal candidiasis in high-risk surgical patients. 98 Cultures of Venous Catheter Tips (VCT) from Intensive Care Unit Patients Stavroula Konstantopoulou, Athanasios Mourikis, Paraskevi Karle...

Expert Review of Anti-infective Therapy

ABSTRACT Introduction: Ventilator-associated pneumonia (VAP) is a common and potentially fatal co... more ABSTRACT Introduction: Ventilator-associated pneumonia (VAP) is a common and potentially fatal complication of mechanical ventilation that is often caused by multidrug-resistant (MDR) Gram-negative bacteria (GNB). Despite the repurposing of older treatments and the novel antimicrobials, many resistance mechanisms cannot be confronted, and novel therapies are needed. Areas covered: We searched the literature for keywords regarding the treatment of GNB infections in mechanically ventilated patients. This narrative review presents new data on antibiotics and non-antibiotic approaches focusing on Phase 3 trials against clinically significant GNB that cause VAP. Expert opinion: Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam stand out as new options for infections by Klebsiella pneumoniae carbapenemase-producing bacteria, whereas ceftolozane-tazobactam adds therapeutic flexibility in Pseudomonas aeruginosa infections with multiple resistance mechanisms. Ceftazidime-avibactam and ceftolozane-tazobactam have relevant literature. Aztreonam-avibactam holds promise for the treatment of infections by metallo-β-lactamase (MBL)-producing organisms. Recently approved cefiderocol possesses an extended antibacterial spectrum, including KPC- and MBL-producers. However, recently published data have toned down optimism about treating VAP caused by carbapenem-resistant Acinetobacter baumannii. For the latter, eravacycline may provide additional hope, pending pertinent data. Non-antibiotic treatments currently being considered as adjunct therapeutic approaches are welcome. Nevertheless, they will hopefully substitute current antimicrobials in the future.

British journal of neurosurgery, 2021

Insertion of an external ventricular drain is a common procedure used in everyday practice by neu... more Insertion of an external ventricular drain is a common procedure used in everyday practice by neurosurgeons all around the world. It consists of the placement of an external ventricular drain (EVD) into the ventricular system providing the ability to measure intracranial pressure, and also divert the flow of cerebrospinal fluid (CSF) in a variety of pathological conditions. The most common complication is infection, and it may result in devastating consequences and negatively affect the outcome of these patients. The Infectious Diseases Society of America (IDSA), the Neurocritical Care Society (NCS), and The Society for Neuroscience in Anesthesiology & Critical Care (SNACC) have published recommendations for the management of EVD-Associated Ventriculitis. The objective of this study was to assess the methodological quality and reporting clarity of these recommendations using the AGREE-II tool. We found that the overall quality of the published clinical practice guidelines is accepta...

Expert Review of Anti-infective Therapy

Staphylococcus aureus is an important human pathogen that affects children worldwide. The number ... more Staphylococcus aureus is an important human pathogen that affects children worldwide. The number of publications discussing community-associated S. aureus infections, particularly in children, adolescents and young adults, has increased in recent years. This is related to the emergence and worldwide spread of community-associated methicillin-resistant S. aureus and the increase in severe life-threatening community-associated S. aureus infections. The increase in severity has been seen with both methicillin-resistant and methicillin-susceptible strains. This suggests that other virulence factors might be associated with the observed trend. Panton-Valentine leukocidin is a distinctive virulence factor associated with a highly aggressive and often fatal form of community-acquired infections. We propose that empiric treatment should be adapted to the type of infection and the resistance profile present in each country or region. In cases of severe infection, a combination of antibiotics, including at least one molecule active against protein synthesis such as clindamycin or linezolid, will be needed.

Cardiovascular Drugs and Therapy

Purpose Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We... more Purpose Low-dose steroids may reduce the mortality of severely ill patients with septic shock. We sought to determine whether exposure to stress-dose steroids during and/or after cardiopulmonary resuscitation is associated with reduced risk of death due to postresuscitation septic shock. Methods We analyzed pooled, individual patient data from two prior, randomized clinical trials (RCTs). RCTs evaluated vasopressin, steroids, and epinephrine (VSE) during resuscitation and stress-dose steroids after resuscitation in vasopressorrequiring, in-hospital cardiac arrest. In the second RCT, 15 control group patients received open-label, stress-dose steroids. Patients with postresuscitation shock were assigned to a Steroids (n = 118) or No Steroids (n = 73) group according to an Bas-treated^principle. We used cumulative incidence competing risks Cox regression to determine cause-specific hazard ratios (CSHRs) for pre-specified predictors of lethal septic shock (primary outcome). In sensitivity analyses, data were analyzed according to the intention-to-treat (ITT) principle (VSE group, n = 103; control group, n = 88). Results Lethal septic shock was less likely in Steroids versus No Steroids group, CSHR, 0.40, 95% confidence interval (CI), 0.20-0.82; p = 0.012. ITT analysis yielded similar results: VSE versus Control, CSHR, 0.44, 95% CI, 0.23-0.87; p = 0.019. Adjustment for significant, between-group baseline differences in composite cardiac arrest causes such as Bhypotension and/or myocardial ischemia^did not appreciably affect the aforementioned CSHRs. Conclusions In this reanalysis, exposure to stress-dose steroids (primarily in the context of a combined VSE intervention) was associated with lower risk of postresuscitation lethal septic shock.

Journal of Intensive Care Medicine

Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdomina... more Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdominal hypertension (IAH). However, despite animal experimentation and physiological studies on humans in favor of this hypothesis, there is no definitive clinical data that IAH is associated with VAP. We therefore aimed to study whether IAH is a risk factor for increased incidence of VAP in critical care patients. This 1-center prospective observational cohort study was conducted in the intensive care unit of the University Hospital of Larissa, Greece, during 2013 to 2015. Consecutive patients were recruited if they presented risk factors for IAH at admission and were evaluated systematically for IAH and VAP for a 28-day period. Results: Forty-five (36.6%) of 123 patients presented IAH and 45 (36.6%) presented VAP; 24 patients presented VAP following IAH. Cox regression analysis showed that VAP was independently associated with IAH (1.06 [1.01-1.11]; P = .053), while there was an indication ...

Cardiovascular Drugs and Therapy

Journal of critical care, Jan 25, 2018

To test the potential of four common Toll-like receptor (TLR) polymorphisms to predispose to spec... more To test the potential of four common Toll-like receptor (TLR) polymorphisms to predispose to specific intensive care unit (ICU)-acquired infections and affect outcomes in a Greek ICU. The incidence of TLR2-Arg753Gln, TLR4-Asp299Gly, TLR4-Thr399Ile and TLR9-T1237C polymorphisms, and their association with ICU-acquired infections and patients' clinical outcomes were prospectively evaluated The examined genetic polymorphisms were assessed by real-time Polymerase-Chain-Reaction (PCR). During a 15-month period, 224 patients were enrolled and genotyped. The prevalence of genetic polymorphisms for TLR4-Asp299Gly, TLR4-Thr399Ile, mixed TLR4-Asp299Gly/Thr399Ile, TLR9-T1237C and TLR2-Arg753Gln was 14.4%, 14.7%, 11.2%, 24.5% and 2.2%, respectively. TLR4 polymorphisms were associated with increased susceptibility towards specific ICU-acquired infections, i.e. Gram-negative central-nervous-system infections (CNSI), ventilator-associated pneumonia (VAP) and urinary-tract infections (UTI), pri...