Timing and Outcomes of Noninvasive Ventilation in 307 ARDS COVID-19 Patients: An Observational Study in an Italian Third Level COVID-19 Hospital.

Background and Objectives: Background: Coronavirus disease 2019 (COVID-19) is a novel cause of Acute Respiratory Distress Syndrome (ARDS). Noninvasive ventilation (NIV) is widely used in patients with ARDS across several etiologies. Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, its use has grown significantly in hospital wards. However, there is a lack of evidence to support the efficacy of NIV in patients with COVID-19 ARDS. Materials and Methods: We conducted an observational cohort study including adult ARDS COVID-19 patients admitted in a third level COVID-center in Rome, Italy. The study analyzed the rate of NIV failure defined by the occurrence of orotracheal intubation and/or death within 28 days from starting NIV, its effectiveness, and the associated relative risk of death. The factors associated with the outcomes were identified through logistic regression analysis. Results: During the study period, a total of 942 COVID-19 patients were admitted to our hospital, of which 307 (32.5%) presented with ARDS at hospitalization. During hospitalization 224 (23.8%) were treated with NIV. NIV failure occurred in 84 (37.5%) patients. At 28 days from starting NIV, moderate and severe ARDS had five-fold and twenty-fold independent increased risk of NIV failure (adjusted odds ratio, aOR = 5.01, 95% CI 2.08−12.09, and 19.95, 95% CI 5.31−74.94), respectively, compared to patients with mild ARDS. A total of 128 patients (13.5%) were admitted to the Intensive Care Unit (ICU). At 28-day from ICU admission, intubated COVID-19 patients treated with early NIV had 40% lower mortality (aOR 0.60, 95% CI 0.25−1.46, p = 0.010) compared with patients that underwent orotracheal intubation without prior NIV. Conclusions: These findings show that NIV failure was independently correlated with the severity category of COVID-19 ARDS. The start of NIV in COVID-19 patients with mild ARDS (P/F > 200 mmHg) appears to increase NIV effectiveness and reduce the risk of orotracheal intubation and/or death. Moreover, early NIV (P/F > 200 mmHg) treatment seems to reduce the risk of ICU mortality at 28 days from ICU admission.

Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study.

BACKGROUND: A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. METHODS: We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. RESULTS: The cohort comprised 577 adults with bloodstream infections (n = 391) or nonbacteremic infections involving mainly the urinary tract, lower respiratory tract, and intra-abdominal structures. All received treatment with CAZ-AVI alone (n = 165) or with ≥1 other active antimicrobials (n = 412). The all-cause mortality rate 30 days after infection onset was 25% (146/577). There was no significant difference in mortality between patients managed with CAZ-AVI alone and those treated with combination regimens (26.1% vs 25.0%, P = .79). In multivariate analysis, mortality was positively associated with presence at infection onset of septic shock (P = .002), neutropenia (P < .001), or an INCREMENT score ≥8 (P = .01); with lower respiratory tract infection (LRTI) (P = .04); and with CAZ-AVI dose adjustment for renal function (P = .01). Mortality was negatively associated with CAZ-AVI administration by prolonged infusion (P = .006). All associations remained significant after propensity score adjustment. CONCLUSIONS: CAZ-AVI is an important option for treating serious KPC-Kp infections, even when used alone. Further study is needed to explore the drug's seemingly more limited efficacy in LRTIs and potential survival benefits of prolonging CAZ-AVI infusions to ≥3 hours.

Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K. pneumoniae.

Background: Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking. Methods: We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic. Results: The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival. Conclusions: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.

Unexpected human cases of cutaneous anthrax in Latium region, Italy, August 2017: integrated human-animal investigation of epidemiological, clinical, microbiological and ecological factors.

On 31 August, a veterinarian and a farmworker were hospitalised for skin lesions. Both had been exposed to a dead cow on 19 August on a farm near Rome, where eight further cattle died of confirmed anthrax later the same month. At admission, the first case showed a black depressed eschar and another smaller lesion on one hand. The second case presented deep infection of the skin, with involvement of both arms. Anthrax diagnosis was confirmed by detection of B. anthracis DNA in eschar fragments from both patients. T-cell specific immunity was studied by flow cytometry and Elispot assay after stimulation with B. anthracis secretome in blood samples collected from Case 1. Immunoglobulin production was detected by complement fixation assay. In Case 1, specific CD4+ T-cell activation was detected, without antibody production. Specific antibodies were detected only in the second patient with severe cutaneous illness. Both patients recovered. The two human anthrax cases were epidemiologically linked, but anthrax was not suspected at admission in either case. The veterinarian had initially unrecognised professional exposure and the exposed farmworker did initially not report exposure to affected animals. A One Health strategy integrating human and animal investigations was essential to confirm the diagnosis.

[Towards an effective assessment of the sustainability of health interventions]. / Verso una misura effettiva della sostenibilità degli interventi sanitari.

In a sluggish economy, cost containment is a central issue for the national health service, and health authorities are increasingly requiring proof of the economic and clinical value of health interventions. In this context, the integration and/or evolution of techniques to measure the economic sustain- ability of new technologies is essential. The disability-adjusted life year (DALY) and quality-adjusted life year (QALY) are two measures used in the assessment of health interventions, which, although based on the same theoretical concept, differ in a number of important aspects. DALY can overcome the limit of using arbitrary economic threshold values since it is a benchmark directly comparable with the GDP per capita, an unbiased measure of sustainability. Indeed, in 2002 the World Health Organization (WHO) suggested that interventions costing less than 3 times the per-capita GDP per DALY averted could be considered cost effective. The Expected Value of Information and an estimate of the contribution to GDP (social costs due to presenteeism and absenteeism), along with Health Technology Assessment-based disinvestment decisions and the generation of a comprehensive health dataset (to be analysed using artificial intelligence) should be implemented. These procedures may improve the effectiveness of health governance and lead to better quality of healthcare services.

Probiotics and infective endocarditis in patients with hereditary hemorrhagic telangiectasia: a clinical case and a review of the literature.

BACKGROUND: In the last decades, probiotics have been widely used as food supplements because of their putative beneficial health effects. They are generally considered safe but rare reports of serious infections caused by bacteria included in the definition of probiotics raise concerns on their potential pathogenic role in patients with particular predisposing factors. Patients with hereditary hemorrhagic telangiectasia (HHT) are exposed to infections because of telangiectasias and arteriovenous malformations (AVMs). We describe what is, to our knowledge, the first case of infective endocarditis (IE) caused by Lactobacillus rhamnosus in a patient with HHT. A systematic review of the relevant medical literature is presented. CASE PRESENTATION: A patient with HHT and an aortic bioprosthesis was admitted because of prolonged fever not responding to antibiotics. The patient had a history of repeated serious infections with hospitalizations and prolonged use of antibiotics, and used to assume large amounts of different commercial products containing probiotics. Weeks before the onset of symptoms the patient had been treated with nasal packings and with surgical closure of a nasal bleeding site because of recurrent epistaxis. A diagnosis of IE of the aortic bioprosthesis was made. All blood coltures were positive for L. rhamnosus. The patients responded to a cycle of 6 weeks of amoxicillin/clavulanate plus gentamicin. A systematic review of IE linked to consumption of probiotics, and of infective endocarditis in patients with HHT was conducted. 10 cases of IE linked to probiotics consumption and 6 cases of IE in patients with HHT were found. CONCLUSIONS: Consumption of probiotics can pose a risk of serious infections in patients with particular predisposing factors. Patients with HHT can be considered at risk because of their predisposition to infections. Prophylaxis with antibiotics before nasal packings in patients with HHT can be considered.

Circulation of blaKPC-3-Carrying IncX3 Plasmids among Citrobacter freundii Isolates in an Italian Hospital.

Colonizations due to carbapenem-resistant Enterobacteriaceae (CRE) are a source of antimicrobial resistance transmission in health care settings. Eleven Citrobacter freundii strains producing KPC-3 carbapenemase were isolated from rectal swabs during a 3-year surveillance program. blaKPC-3-carrying plasmids were found to belong to the IncX3 group in 9 of the 11 strains, and complete nucleotide sequences were obtained for 2 of them. Our results highlight the possible role of C. freundii as reservoir of resistance genes.

Isolation of KPC 3-producing Enterobacter aerogenes in a patient colonized by MDR Klebsiella pneumoniae.

We describe the interspecies transmission of the plasmid-mediated blaKPC-3 gene, which confers carbapenem resistance, between clinically relevant gram-negative bacteria in a single patient. A KPC-3 producing Enterobacter aerogenes was isolated from a hospitalized patient previously colonized and then infected by a Klebsiella pneumoniae ST101 carrying the blaKPC-3 gene. The strains showed identical plasmids. Since intense horizontal exchanges among bacteria can occur in the gut, clinicians should be aware that patients colonized by carbapenem-resistant K. pneumoniae could become carriers of other carbapenem-resistant Enterobacteriaceae.

Cost-Effectiveness Analysis of Universal Human Papillomavirus Vaccination Using a Dynamic Bayesian Methodology: The BEST II Study.

BACKGROUND: Human papillomavirus (HPV) plays a role in the development of benign and malign neoplasms in both sexes. The Italian recommendations for HPV vaccines consider only females. The BEST II study (Bayesian modelling to assess the Effectiveness of a vaccination Strategy to prevent HPV-related diseases) evaluates 1) the cost-effectiveness of immunization strategies targeting universal vaccination compared with cervical cancer screening and female-only vaccination and 2) the economic impact of immunization on various HPV-induced diseases. OBJECTIVE: The objective of this study was to evaluate whether female-only vaccination or universal vaccination is the most cost-effective intervention against HPV. METHODS: We present a dynamic Bayesian Markov model to investigate transmission dynamics in cohorts of females and males in a follow-up period of 55 years. We assumed that quadrivalent vaccination (against HPV 16, 18, 6, and 11) is available for 12-year-old individuals. The model accounts for the progression of subjects across HPV-induced health states (cervical, vaginal, vulvar, anal, penile, and head/neck cancer as well as anogenital warts). The sexual mixing is modeled on the basis of age-, sex-, and sexual behavioral-specific matrices to obtain the dynamic force of infection. RESULTS: In comparison to cervical cancer screening, universal vaccination results in an incremental cost-effectiveness ratio of €1,500. When universal immunization is compared with female-only vaccination, it is cost-effective with an incremental cost-effectiveness ratio of €11,600. Probabilistic sensitivity analysis shows a relatively large amount of parameter uncertainty, which interestingly has, however, no substantial impact on the decision-making process. The intervention being assessed seems to be associated with an attractive cost-effectiveness profile. CONCLUSIONS: Universal HPV vaccination is found to be a cost-effective choice when compared with either cervical cancer screening or female-only vaccination within the Italian context.

Pragmemes revisited. A theoretical framework.

In this paper, we take up an old issue that of pragmemes, broached by Mey and further explored by Capone. It is not easy to define pragmemes and distinguish them sufficiently from speech acts (units of language use broached by Austin and Searle) or from Wittgensteinian language games or from macro speech acts (see van Dijk on macrostructures) or from Goffman's scripts. The best idea we could develop about pragmemes is that they instantiate the triple articulation of language, proposed by Jock Wong; being essentially composed of phonological-syntactic units, that have a certain content relative to a social situation and to a certain culture, pragmemes express a certain function (or illocutionary force), like, e.g., modifying society or some aspect of it. They are part of a chapter that can be called either "societal pragmatics" or "emancipatory pragmatics," to use the words by Mey. In fact, knowledge of how language is used to diminish the rights of people and to propagate the "status quo" may be instrumental to give rights and power to ordinary human beings who are oppressed by political and economical structures.

The impact of armed conflict on the development and global spread of antibiotic resistance: a systematic review.

BACKGROUND: Scant data are available on the link between armed conflicts and the development and spread of antimicrobial resistance. OBJECTIVES: We performed a systematic review with the aim to summarize the available data on the prevalence and features of antibiotic resistance and the causes of antibiotic resistance development during armed conflicts in the 21st century. METHODS: Data sources: PubMed and SCOPUS databases were searched from 1 January 2000 to 30 November 2023. STUDY ELIGIBILITY CRITERIA: Original articles reporting data on armed conflicts and antimicrobial resistance were included in this systematic review. No attempt was made to obtain information from unpublished studies. No language restriction was applied. Methods of data synthesis: Both quantitative and qualitative information were summarized by means of textual descriptions. PARTICIPANTS: Patients or soldiers deployed in armed conflict zones. TESTS: culture-dependent antibiotic sensitivity testing or molecular detection of the genetic determinants of antibiotic resistance after a confirmed diagnosis of bacterial infection. Assessment of risk of bias: To evaluate the quality of the included studies, we adapted the tool recommended by the Joanna Briggs Institute. RESULTS: Thirty-four studies were identified, published between November 2004 and November 2023. The quality of included studies was high and medium in 47% and 53% of the studies, respectively. The included studies reported high infection and colonization rates of multidrug-resistant bacteria. Studies performed during the Eastern Ukraine conflict reported high rates of New Delhi metallo-ß-lactamase producers. DISCUSSION: Our findings confirm that wars lead to a large pool of multidrug-resistant infections that could potentially spread. Infection control in healthcare facilities in conflict zones and proper antimicrobial stewardship are crucial.

Outcomes and Predictors of Mortality in Patients With KPC-Kp Infections Treated With Meropenem Vaborbactam: An Observational Multicenter Study.

Background: Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam. Methods: We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24 hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality. Results: The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48 hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48 hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy. Conclusions: Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy.

Daptomycin for the treatment of infective endocarditis: results from a European registry.

OBJECTIVES: Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010. PATIENTS AND METHODS: Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery. RESULTS: Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed. CONCLUSIONS: In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation.

Reversion to susceptibility of a carbapenem-resistant clinical isolate of Klebsiella pneumoniae producing KPC-3.

OBJECTIVES: We report the case of a kidney-transplant patient, suffering an intra-abdominal abscess at the surgical site caused by a carbapenem-resistant ST258 Klebsiella pneumoniae clone, producing the KPC-3 carbapenemase. Under tigecycline treatment, the patient developed a sepsis caused by a carbapenem-susceptible ST258 K. pneumoniae strain. Complete DNA sequences of the plasmids carried by the resistant and susceptible strains from this patient were determined. METHODS: The complete DNA sequences of plasmids were obtained by applying the 454 Genome Sequencer FLX-PLUS procedure on a library constructed of total plasmid DNA purified from the carbapenem-resistant and -susceptible strains. RESULTS: In the carbapenem-resistant strain, four plasmids encoding 24 resistance genes, including blaKPC-3, and two putative virulence clusters were detected. In the susceptible strain, large rearrangements occurred in the KPC-carrying plasmid, causing the deletion of the entire Tn4401::blaKPC-3 transposon, with the consequent reversion of the strain to carbapenem susceptibility. The patient was successfully treated with carbapenems and fully recovered. CONCLUSIONS: The description of the plasmid content in these two strains gives interesting insights into the plasticity of KPC-carrying plasmids in K. pneumoniae.

Perspectives on the semantics/pragmatics debate: insights from aphasia research.

In the philosophy of language, there are many ongoing controversies that stem from relying too heavily on an utterance-based framework. The traditional approach of rigidly partitioning the utterance's meaning into what is grammatically determined from what is not may not fully capture the complexity of human language in real-world communicative contexts. To address this issue, we suggest shifting focus toward a broader analysis level encompassing conversations and discourses. From this broader perspective, it is possible to obtain a more integrated view of how linguistic and extra-linguistic aspects dynamically interact and thus reconsider semantics/pragmatics dichotomy as complementary dimensions. Meaning is not confined to linguistic structures alone but emerges from the dynamic interplay of words, sociocultural knowledge, discursive situations, and psychological dispositions of speakers. Substantiating this perspective calls for embracing an interdisciplinary approach that synthesizes research from various domains, including linguistics, cognitive psychology, and philosophy of language. This paper focuses on a particularly compelling case study: aphasia. Speeches produced by individuals with aphasia represent complex scenarios where the balance between linguistic and extra-linguistic aspects is notably compromised, often to the former's detriment. Aphasics' productions represent a vivid example of how the interpretation of speeches can be far from involving fixed and static operations. Instead, it entails continuously reallocating cognitive resources toward the most readily available and accessible sources for the speakers. This case study ultimately demonstrates that the influence of semantic and pragmatic processes in shaping and conveying meanings displays remarkable adaptability, continuously adjusting to the ever changing demands placed upon speakers.

Streptococcus intermedius Brain Abscess with Lung Abscess and Aortic Valve Endocarditis: A Case Report and Literature Review.

Streptococcus intermedius is frequently associated with brain and liver abscesses, while pleuropulmonary infections are considered rarer. Even less frequent is the association of lung and brain abscesses due to this agent with infective endocarditis. We describe the case of a 40-year-old man complaining of cough, fever, and headache who was diagnosed with a brain abscess due to S. intermedius, a concomitant lung abscess, and aortic native valve endocarditis. He was treated with surgical drainage of the brain abscess and a 4-week course of intravenous ceftriaxone, followed by oral amoxicillin/clavulanate, obtaining healing of the lesions without relapse of the infection.

Novel health economic evaluation of a vaccination strategy to prevent HPV-related diseases: the BEST study.

BACKGROUND: The development of human papillomavirus (HPV)-related diseases is not understood perfectly and uncertainties associated with commonly utilized probabilistic models must be considered. The study assessed the cost-effectiveness of a quadrivalent-based multicohort HPV vaccination strategy within a Bayesian framework. METHODS: A full Bayesian multicohort Markov model was used, in which all unknown quantities were associated with suitable probability distributions reflecting the state of currently available knowledge. These distributions were informed by observed data or expert opinion. The model cycle lasted 1 year, whereas the follow-up time horizon was 90 years. Precancerous cervical lesions, cervical cancers, and anogenital warts were considered as outcomes. RESULTS: The base case scenario (2 cohorts of girls aged 12 and 15 y) and other multicohort vaccination strategies (additional cohorts aged 18 and 25 y) were cost-effective, with a discounted cost per quality-adjusted life-year gained that corresponded to €12,013, €13,232, and €15,890 for vaccination programs based on 2, 3, and 4 cohorts, respectively. With multicohort vaccination strategies, the reduction in the number of HPV-related events occurred earlier (range, 3.8-6.4 y) when compared with a single cohort. The analysis of the expected value of information showed that the results of the model were subject to limited uncertainty (cost per patient = €12.6). CONCLUSIONS: This methodological approach is designed to incorporate the uncertainty associated with HPV vaccination. Modeling the cost-effectiveness of a multicohort vaccination program with Bayesian statistics confirmed the value for money of quadrivalent-based HPV vaccination. The expected value of information gave the most appropriate and feasible representation of the true value of this program.

Epidemiology, Clinical Presentation and Treatment of Non-Hepatic Hyperammonemia in ICU COVID-19 Patients.

(1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data. Logistic regression analyses were performed to identify predictors of NHH; (3) Results: 156 COVID-19 patients were admitted to the ICU. The incidence of NHH was 12.2% (19 patients). The univariate analysis showed that invasive mechanical ventilation had a 6.6-fold higher risk (OR 6.66, 95% CI 0.86-51.6, p = 0.039) for NHH, while in the multiple regression analysis, there was a 7-fold higher risk for NHH-but it was not statistically significant (OR 7.1, 95% CI 0.90-56.4, p = 0.062). Demographics, clinical characteristics and mortality in the ICU at 28 days did not show a significant association with NHH. (4) Conclusions: The incidence of NHH in ICU COVID-19 patients was not low. NHH did not appear to significantly increase mortality, and all patients with non-hepatic hyperammonemia were successfully treated without further complications. However, the pathogenesis of NHH in ICU patients with COVID-19 remains a topic to be explored with further research.

Epidemiology of ventilator-associated pneumonia in ICU COVID-19 patients: an alarming high rate of multidrug-resistant bacteria.

BACKGROUND: COVID­19 is a novel cause of acute respiratory distress syndrome (ARDS) that leads patients to intensive care unit (ICU) admission requiring invasive ventilation, who consequently are at risk of developing of ventilator­associated pneumonia (VAP). The aim of this study was to assess the incidence, antimicrobial resistance, risk factors, and outcome of VAP in ICU COVID-19 patients in invasive mechanical ventilation (MV). METHODS: Observational prospective study including adult ICU admissions between January 1, 2021, and June 31, 2021, with confirmed COVID-19 diagnosis were recorded daily, including demographics, medical history, ICU clinical data, etiology of VAPs, and the outcome. The diagnosis of VAP was based on multi-criteria decision analysis which included a combination of radiological, clinical, and microbiological criteria in ICU patients in MV for at least 48 h. RESULTS: Two hundred eighty-four COVID-19 patients in MV were admitted in ICU. Ninety-four patients (33%) had VAP during the ICU stay, of which 85 had a single episode of VAP and 9 multiple episodes. The median time of onset of VAP from intubation were 8 days (IQR, 5-13). The overall incidence of VAP was of 13.48 episodes per 1000 days in MV. The main etiological agent was Pseudomonas aeruginosa (39.8% of all VAPs) followed by Klebsiella spp. (16.5%); of them, 41.4% and 17.6% were carbapenem resistant, respectively. Patients during the mechanical ventilation in orotracheal intubation (OTI) had a higher incidence than those in tracheostomy, 16.46 and 9.8 episodes per 1000-MV day, respectively. An increased risk of VAP was reported in patients receiving blood transfusion (OR 2.13, 95% CI 1.26-3.59, p = 0.005) or therapy with Tocilizumab/Sarilumab (OR 2.08, 95% CI 1.12-3.84, p = 0.02). The pronation and PaO2/FiO2 ratio at ICU admission were not significantly associated with the development of VAPs. Furthermore, VAP episodes did not increase the risk of death in ICU COVID-19 patients. CONCLUSIONS: COVID-19 patients have a higher incidence of VAP compared to the general ICU population, but it is similar to that of ICU ARDS patients in the pre-COVID-19 period. Interleukin-6 inhibitors and blood transfusions may increase the risk of VAP. The widespread use of empirical antibiotics in these patients should be avoided to reduce the selecting pressure on the growth of multidrug-resistant bacteria by implementing infection control measures and antimicrobial stewardship programs even before ICU admission.