The recent expansion of multidrug resistant and pan-drug-resistant pathogens poses significant challenges in the treatment of healthcare associated infections. An important advancement, is a handful ...of recently launched new antibiotics targeting some of the current most problematic Gram-negative pathogens, namely carbapenem-producing Enterobacteriaceae (CRE) and carbapenem-resistant
(CRPA). Less options are available against carbapenem-resistant
(CRAB) and strains producing metallo-beta lactamases (MBL). Ceftazidime-avibactam signaled a turning point in the treatment of KPC and partly OXA- type carbapenemases, whereas meropenem-vaborbactam was added as a potent combination against KPC-producers. Ceftolozane-tazobactam could be seen as an ideal beta-lactam backbone for the treatment of CRPA. Plazomicin, an aminoglycoside with better pharmacokinetics and less toxicity compared to other class members, will cover important proportions of multi-drug resistant pathogens. Eravacycline holds promise in the treatment of infections by CRAB, with a broad spectrum of activity similar to tigecycline, and improved pharmacokinetics. Novel drugs and combinations are not to be considered "panacea" for the ongoing crisis in the therapy of XDR Gram-negative bacteria and colistin will continue to be considered as a fundamental companion drug for the treatment of carbapenem-resistant Enterobacteriaceae (particularly in areas where MBL predominate), for the treatment of CRPA (in many cases being the only
active drug) as well as CRAB. Aminoglycosides are still important companion antibiotics. Finally, fosfomycin as part of combination treatment for CRE infections and
, deserves a greater attention. Optimal conditions for monotherapy and the "when and how" of combination treatments integrating the novel agents will be discussed.
Clinical evidence suggests that nebulized colistimethate sodium (CMS) has benefits for treating lower respiratory tract infections caused by multidrug-resistant Gram-negative bacteria (GNB). Colistin ...is positively charged, while CMS is negatively charged, and both have a high molecular mass and are hydrophilic. These physico-chemical characteristics impair crossing of the alveolo-capillary membrane but enable the disruption of the bacterial wall of GNB and the aggregation of the circulating lipopolysaccharide. Intravenous CMS is rapidly cleared by glomerular filtration and tubular excretion, and 20–25% is spontaneously hydrolyzed to colistin. Urine colistin is substantially reabsorbed by tubular cells and eliminated by biliary excretion. Colistin is a concentration-dependent antibiotic with post-antibiotic and inoculum effects. As CMS conversion to colistin is slower than its renal clearance, intravenous administration can lead to low plasma and lung colistin concentrations that risk treatment failure. Following nebulization of high doses, colistin (200,000 international units/24h) lung tissue concentrations are > five times minimum inhibitory concentration (MIC) of GNB in regions with multiple foci of bronchopneumonia and in the range of MIC breakpoints in regions with confluent pneumonia. Future research should include: (1) experimental studies using lung microdialysis to assess the PK/PD in the interstitial fluid of the lung following nebulization of high doses of colistin; (2) superiority multicenter randomized controlled trials comparing nebulized and intravenous CMS in patients with pandrug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis; (3) non-inferiority multicenter randomized controlled trials comparing nebulized CMS to intravenous new cephalosporines/ß-lactamase inhibitors in patients with extensive drug-resistant GNB ventilator-associated pneumonia and ventilator-associated tracheobronchitis.
•IVDA and HIV patients with IE emerged during the era of economic crisis.•S. aureus and MRSA predominated in the youth and Enterococci in the elderly.•Compared to previous cohort, rheumatic fever ...decreases and renal disease increases.•Both cardiac surgery and compliance with antimicrobial treatment promoted survival.
The clinical profile, management and outcome of infective endocarditis (IE) may be influenced by socioeconomic issues.
A nationwide prospective study evaluated IE during the era of deep economic crisis in Greece. Epidemiological data and factors associated with 60-day mortality were analyzed through descriptive statistics, logistic and Cox-regression models.
Among 224 patients (male 72.3%, mean age 62.4 years), Staphylococcus aureus (n = 62; methicillin-resistant S. aureus (MRSA) 33.8%) predominated in the young without impact on mortality (p = 0.593), whilst Enterococci (n = 36) predominated in the elderly. Complications of IE were associated with mortality: heart failure OR 2.415 (95% CI: 1.159–5.029), p = 0.019, stroke OR 3.206 (95% CI: 1.190–8.632), p = 0.018 and acute kidney injury OR 2.283 (95% CI: 1.085–4.805), p = 0.029. A 60-day survival benefit was solely related to cardiac surgery for IE during hospitalization HR 0.386 (95% CI: 0.165–0.903), p = 0.028 and compliance with antimicrobial treatment guidelines HR 0.487 (95% CI: 0.259–0.916), p = 0.026. Compared with a previous country cohort study, history of rheumatic fever and native valve predisposition had declined, whilst underlying renal disease and right-sided IE had increased (p < 0.0001); HIV infection had emerged (p = 0.002). No difference in rates of surgery and outcome was assessed.
A country-wide survey of IE highlighted emergence of HIV, right-sided IE and predominance of MRSA in the youth during a severe socioeconomic crisis. Compliance with treatment guidelines promoted survival.
Stewart's approach is known to have better diagnostic accuracy for the identification of metabolic acid-base disturbances compared to traditional methods based either on plasma bicarbonate ...concentration (HCO
) and anion gap (AG) or on base excess/deficit (BE). This study aimed to identify metabolic acid-base disorders using either Stewart's or traditional approaches in critically ill COVID-19 patients admitted to the ICU, to recognize potential hidden acid-base metabolic abnormalities and to assess the prognostic value of these abnormalities for patient outcome.
This was a single-center retrospective study, in which we collected data from patients with severe COVID-19 admitted to the ICU. Electronical files were used to retrieve data for arterial blood gases, serum electrolytes, and proteins and to derive HCO
, BE, anion gap (AG), AG adjusted for albumin (AG
), strong ion difference, strong ion gap (SIG), and SIG corrected for water excess/deficit (SIG
). The acid-base status was evaluated in each patient using the BE, HCO
, and physicochemical approaches.
We included 185 patients. The physicochemical approach detected more individuals with metabolic acid-base abnormalities than the BE and HCO
approaches (
< 0.001), and at least one acid-base disorder was recognized in most patients. According to the physicochemical method, 170/185 patients (91.4%) had at least one disorder, as opposed to the number of patients identified using the BE 90/186 (48%) and HCO
62/186 (33%) methods. Regarding the derived acid-base status variables, non-survivors had greater AG
, (
= 0.013) and SIG
(
= 0.035) compared to survivors.
The identification of hidden acid-base disturbances may provide a detailed understanding of the underlying conditions in patients and of the possible pathophysiological mechanisms implicated. The association of these acid-base abnormalities with mortality provides the opportunity to recognize patients at increased risk of death and support them accordingly.
Background: Rising antimicrobial resistance has led to a revived interest in inhaled colistin treatment in the critically ill patient with ventilator-associated respiratory infection (VARI). ...Nebulization via vibrating mesh nebulizers (VMNs) is considered the current standard-of-care, yet the use of generic jet nebulizers (JNs) is more widespread. Few data exist on the intrapulmonary pharmacokinetics of colistin when administered through VMNs, while there is a complete paucity regarding the use of JNs. Methods: In this study, 18 VARI patients who received 2 million international units of inhaled colistimethate sodium (CMS) through a VMN were pharmacokinetically compared with six VARI patients who received the same drug dose through a JN, in the absence of systemic CMS administration. Results: Surprisingly, VMN and JN led to comparable formed colistin exposures in the epithelial lining fluid (ELF) (median (IQR) AUC0–24: 86.2 (46.0–185.9) mg/L∙h with VMN and 91.5 (78.1–110.3) mg/L∙h with JN). The maximum ELF concentration was 10.4 (4.7–22.6) mg/L and 7.4 (6.2–10.3) mg/L, respectively. Conclusions: Based on our results, JN might be considered a viable alternative to the theoretically superior VMN. Therapeutic drug monitoring in the ELF can be advised due to the observed low exposure, high variability, and appreciable systemic absorption.
•Pericardial effusion with acute cardiac tamponade may be a potential complication of severe SARS-CoV-2 infection.•This should be kept in mind especially when facing mechanically ventilated patients ...with acute hemodynamic collapse.•Bedside TTE is a valuable tool for prompt diagnosis and life-saving therapeutic pericardiocentesis.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently evolved as a pandemic disease. Although the respiratory system is predominantly affected, cardiovascular complications have been frequently identified, including acute myocarditis, myocardial infarction, acute heart failure, arrhythmias and venous thromboembolic events. Pericardial disease has been rarely reported. We present a case of acute life-threatening cardiac tamponade caused by a small pericardial effusion in a mechanically ventilated patient with severe COVID-19 associated pneumonia. The patient presented acute circulatory collapse with hemodynamic features of cardiogenic or obstructive shock. Bedside echocardiography permitted prompt diagnosis and life-saving pericardiocentesis. Further investigation revealed no other apparent cause of pericardial effusion except for SARS-CoV-2 infection. Cardiac tamponade may complicate COVID-19 and should be included in the differential diagnosis of acute hemodynamic deterioration in mechanically ventilated COVID-19 patients.
We describe a critically ill, SARS-CoV-2 positive patient with respiratory failure and thrombotic/livedoid skin lesions, appearing during the course of the disease. The biopsy of the lesions revealed ...an occlusive, pauci-inflammatory vasculopathy of the cutaneous small vessels characterized by complement and fibrinogen deposition on vascular walls, pointing to a thrombotic vasculopathy. Transmission electron microscopy of the affected skin failed to reveal any viral inclusions. Clinical evaluation and laboratory findings ruled out systemic coagulopathies and disseminated intravascular coagulation, drug-induced skin reaction, and common viral rashes. Our hypothesis is that the, herein evidenced, microvascular occlusive injury might constitute a significant pathologic mechanism in COVID-19, being a common denominator between cutaneous and pulmonary manifestations.
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