Infections with
have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. The major problem leading to high mortality lies in the ...appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. Diverse strategies range from killing (new antibiotics) to disarming (antivirulence) the pathogen. In this review, selected aspects of
antimicrobial resistance and infection management will be addressed. Many studies have been performed to evaluate the risk factors for resistance and the potential consequences on mortality and attributable mortality. The review also looks at the mechanisms associated with resistance -
is a pathogen presenting a large genome, and it can develop a large number of factors associated with antibiotic resistance involving almost all classes of antibiotics. Clinical approaches to patients with bacteremia, ventilator-associated pneumonia, urinary tract infections and skin soft tissue infections are discussed. Antibiotic combinations are reviewed as well as an analysis of pharmacokinetic and pharmacodynamic parameters to optimize
treatment. Limitations of current therapies, the potential for alternative drugs and new therapeutic options are also discussed.
The treatment of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections in critically ill patients presents many challenges. Since an effective treatment should be administered as soon as ...possible, resistance to many antimicrobial classes almost invariably reduces the probability of adequate empirical coverage, with possible unfavorable consequences. In this light, readily available patient's medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and firmly guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. Rapid diagnostics and efficient laboratory workflows are also of paramount importance both for anticipating diagnosis and for rapidly narrowing the antimicrobial spectrum, with de-escalation purposes and in line with antimicrobial stewardship principles. Carbapenem-resistant Enterobacteriaceae,
, and
are being reported with increasing frequencies worldwide, although with important variability across regions, hospitals and even single wards. In the past few years, new treatment options, such as ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, plazomicin, and eravacycline have become available, and others will become soon, which have provided some much-awaited resources for effectively counteracting severe infections due to these organisms. However, their optimal use should be guaranteed in the long term, for delaying as much as possible the emergence and diffusion of resistance to novel agents. Despite important progresses, pharmacokinetic/pharmacodynamic optimization of dosages and treatment duration in critically ill patients has still some areas of uncertainty requiring further study, that should take into account also resistance selection as a major endpoint. Treatment of severe MDR-GNB infections in critically ill patients in the near future will require an expert and complex clinical reasoning, of course taking into account the peculiar characteristics of the target population, but also the need for adequate empirical coverage and the more and more specific enzyme-level activity of novel antimicrobials with respect to the different resistance mechanisms of MDR-GNB.
•Chest CT patterns in COVID-19 may be divided into three main phenotypes with different characteristics o In phenotype 1, respiratory mechanics are consistent with high pulmonary compliance and ...severe hypoxemia.•In phenotype 2, moderate to high PEEP as well as lateral and/or prone positioning may help recruit collapsed areas.•Phenotype 3 resembles typical ARDS and should be managed as such.•Attention should be paid to the risk of pulmonary embolism, regardless of phenotype.
Coronavirus disease 2019 (COVID-19) can cause severe respiratory failure requiring mechanical ventilation. The abnormalities observed on chest computed tomography (CT) and the clinical presentation of COVID-19 patients are not always like those of typical acute respiratory distress syndrome (ARDS) and can change over time. This manuscript aimed to provide brief guidance for respiratory management of COVID-19 patients before, during, and after mechanical ventilation, based on the recent literature and on our direct experience with this population. We identify that chest CT patterns in COVID-19 may be divided into three main phenotypes: 1) multiple, focal, possibly overperfused ground-glass opacities; 2) inhomogeneously distributed atelectasis; and 3) a patchy, ARDS-like pattern. Each phenotype can benefit from different treatments and ventilator settings. Also, peripheral macro- and microemboli are common, and attention should be paid to the risk of pulmonary embolism. We suggest use of personalized mechanical ventilation strategies based on respiratory mechanics and chest CT patterns. Further research is warranted to confirm our hypothesis.
Introduction Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited ...evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. Methods This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24.sup.th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HR.sub.OW). Results Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO.sub.2 /FiO.sub.2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HR.sub.OW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HR.sub.OW 0.41, 95%CI: 0.19-0.89, p = 0.025. Conclusion Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.
We studied 19 cases of proven/probable mucormycosis diagnosed from 2007 to 2015 in our hospital and assessed the microbiological characteristics of the isolates. We recorded the incidence of ...mucormycosis and clinical and microbiological data of infected patients. Isolates were identified to molecular level and tested for their antifungal susceptibility to azoles, amphotericin B, and liposomal amphotericin B according to the CLSI M-38 A2 procedure. The incidence of mucormycosis in cases/100,000 hospital admissions during 2007-2015 increased significantly with respect to that reported in 1988-2006 (3.3 vs. 1.2; P<0.05). Patients mainly had hematological malignancies (52.6%) and/or trauma/surgical wounds (52.6%) and had received antifungal agents before the diagnosis of mucormycosis in 68% of cases. Diagnosis was by isolation (n = 17/19) and/or direct staining (n = 17/18) of Mucorales fungi in clinical samples. Identification was by panfungal PCR in patients with negative results in culture and in direct staining. The microorganisms identified were Lichtheimia spp. (42%), Rhizopus spp. (21%), Cunninghamella bertholletiae (16%), and others (21%). Liposomal amphotericin B was always more active than the other drugs against all the microorganisms except C. bertholletiae. All patients received antifungal treatment with 1 or more antifungal agents, mainly liposomal amphotericin B (17/19). Mortality was 47.4%, although this was significantly lower in the 11 patients in whom debridement was performed (18% vs. 87.5%) (P = 0.015). The incidence of mucormycosis has risen in recent years. The proportion of cases with soft tissue involvement was high, and Lichtheimia was the most frequently involved species. The highest antifungal activity was observed with liposomal amphotericin B.
Summary
During recent years, inappropriate antifungal use has contributed to the global increase in antifungal resistance and has played a role in the shift in the aetiology of invasive fungal ...infections. Moreover, overuse of antifungals may also lead to higher toxicity associated with unnecessary medication exposure and to increased healthcare costs. Antifungal stewardship (AFS) programmes consist of multidisciplinary interventions, led by specialists in infectious disease, microbiology and pharmacy that cooperate and communicate with the major prescribing departments in order to optimise antifungal therapies evaluating the indication, dose, streamlining and duration. Herein, we review the available evidence for the use of AFS and their impact on health economics. We also describe our AFS program, the successive steps we followed and the main difficulties we found.
New antibiotics for Gram-negative pneumonia Bassetti, Matteo; Magnè, Federica; Giacobbe, Daniele Roberto ...
European respiratory review,
12/2022, Volume:
31, Issue:
166
Journal Article
Peer reviewed
Open access
Pneumonia is frequently encountered in clinical practice, and Gram-negative bacilli constitute a significant proportion of its aetiology, especially when it is acquired in a hospital setting. With ...the alarming global rise in multidrug resistance in Gram-negative bacilli, antibiotic therapy for treating patients with pneumonia is challenging and must be guided by
susceptibility results. In this review, we provide an overview of antibiotics newly approved for the treatment of pneumonia caused by Gram-negative bacilli. Ceftazidime-avibactam, imipenem-relebactam and meropenem-vaborbactam have potent activity against some of the carbapenem-resistant Enterobacterales, especially
carbapenemase producers. Several novel antibiotics have potent activity against multidrug-resistant
, such as ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relabactam and cefiderocol. Cefiderocol may also play an important role in the management of pneumonia caused by
, along with plazomicin and eravacycline.
There is a paucity of data concerning the optimal ventilator management in patients with COVID-19 pneumonia; particularly, the optimal levels of positive-end expiratory pressure (PEEP) are unknown. ...We aimed to investigate the effects of two levels of PEEP on alveolar recruitment in critically ill patients with severe COVID-19 pneumonia.
A single-center cohort study was conducted in a 39-bed intensive care unit at a university-affiliated hospital in Genoa, Italy. Chest computed tomography (CT) was performed to quantify aeration at 8 and 16 cmH
O PEEP. The primary endpoint was the amount of alveolar recruitment, defined as the change in the non-aerated compartment at the two PEEP levels on CT scan.
Forty-two patients were included in this analysis. Alveolar recruitment was median interquartile range 2.7 0.7-4.5 % of lung weight and was not associated with excess lung weight, PaO
/FiO
ratio, respiratory system compliance, inflammatory and thrombophilia markers. Patients in the upper quartile of recruitment (recruiters), compared to non-recruiters, had comparable clinical characteristics, lung weight and gas volume. Alveolar recruitment was not different in patients with lower versus higher respiratory system compliance. In a subgroup of 20 patients with available gas exchange data, increasing PEEP decreased respiratory system compliance (median difference, MD - 9 ml/cmH
O, 95% CI from - 12 to - 6 ml/cmH
O, p < 0.001) and the ventilatory ratio (MD - 0.1, 95% CI from - 0.3 to - 0.1, p = 0.003), increased PaO
with FiO
= 0.5 (MD 24 mmHg, 95% CI from 12 to 51 mmHg, p < 0.001), but did not change PaO
with FiO
= 1.0 (MD 7 mmHg, 95% CI from - 12 to 49 mmHg, p = 0.313). Moreover, alveolar recruitment was not correlated with improvement of oxygenation or venous admixture.
In patients with severe COVID-19 pneumonia, higher PEEP resulted in limited alveolar recruitment. These findings suggest limiting PEEP strictly to the values necessary to maintain oxygenation, thus avoiding the use of higher PEEP levels.
In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no ...data available regarding cerebral oxygenation and hemodynamics.
This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO
) removal (ECCO
R). Arterial blood gas values (oxygen saturation SpO
, partial pressure of oxygen PaO
and of carbon dioxide PaCO
) and cerebral oxygenation (rSO
) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients.
Forty-five rescue therapies were performed in 22 patients. The median interquartile range age of the population was 62 57-69 years, and 18/22 82% were male. After RMs, no significant changes were observed in systemic PaO
and PaCO
values, but cerebral oxygenation decreased significantly (52 51-54% vs. 49 47-50%, p < 0.001). After PP, a significant increase was observed in PaO
(from 62 56-71 to 82 76-87 mmHg, p = 0.005) and rSO
(from 53 52-54% to 60 59-64%, p = 0.005). The use of iNO increased PaO
(from 65 67-73 to 72 67-73 mmHg, p = 0.015) and rSO
(from 53 51-56% to 57 55-59%, p = 0.007). The use of ECCO
R decreased PaO
(from 75 75-79 to 64 60-70 mmHg, p = 0.009), with reduction of rSO
values (59 56-65% vs. 56 53-62%, p = 0.002). In the whole population, a significant relationship was found between SpO
and rSO
(R = 0.62, p < 0.001) and between PaO
and rSO
(R0 0.54, p < 0.001).
Rescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs. Registration The study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).
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