UNASSIGNED: Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection (HAI). HAP is associated with a high burden of morbidity and mortality, but the diagnosis is difficult to establish and the incidence uncertain.
UNASSIGNED: Patients aged ≥ 18 years hospitalised with radiologically verified non-ventilator hospital acquired pneumonia (NV-HAP) during 2018 were retrospectively identified at Drammen Hospital, a Norwegian general hospital. Infectious Diseases Society of America and the American Thoracic Society\'s definition of HAP was used.
UNASSIGNED: In total 119 cases of NV-HAP were identified among 27,701 admissions. The incidence was 4.3 per 1000 admissions and 1.2 per 1000 patient-days. The median age was 74 years, 63% were male and median Charlson comorbidity index was 5. Coronary heart disease (42%) was the most common comorbidity. Median length of stay was 17.2 days. A blood culture was obtained in 53.8% of patients, while samples from lower airways were seldom obtained (10.9%). In-hospital mortality was 21%, accumulated 30-day mortality was 27.7% and accumulated 1-year mortality was 39.5%. Thirty-day readmission rate among survivors was 39.4%.
UNASSIGNED: NV-HAP was present in approximately 1 in 250 hospitalisations, most had multiple comorbidities, and 1 in 5 died in hospital. Although thorough microbiological sampling is recommended when NV-HAP is suspected, our data indicate that airway sampling is infrequent in clinical practice. Our findings underscore the need to develop microbiological diagnostic strategies to achieve targeted antimicrobial treatment that may improve patient outcomes and reduce broad-spectrum antibiotic usage.

OBJECTIVE: This study analyzed the risk and impact of developing pneumogenic bacteremia in patients with CRAB nosocomial pneumonia in ICU.
METHODS: This is multicenter retrospective study. Clinical outcomes were compared between bacteremia and non-bacteremia group, and the risk factors for mortality and developing pneumogenic CRAB bacteremia were analyzed.
RESULTS: After patient recruitment, 164 cases were in the bacteremia group, and 519 cases were in the non-bacteremia group. The bacteremia group had 22.4 percentage of increase in-hospital mortality than the non-bacteremia group (68.3% vs 45.9%, P < 0.001). Multivariate analysis showed bacteremia was an independent risk factor for in-hospital mortality (aHR = 2.399, P < 0.001). A long time-interval between ICU admission and pneumonia onset was an independent risk factor for developing bacteremia (aOR = 1.040, P = < 0.001). Spearman\'s rank correlation analysis indicated a high correlation between the days from ICU admission to pneumonia onset and the days of ventilator use before pneumonia onset (correlation coefficient (ρ) = 0.777).
CONCLUSIONS: In patients with CRAB nosocomial pneumonia, bacteremia increased the in-hospital mortality, and a longer interval from ICU admission to pneumonia onset was an independent risk factor for developing bacteremia, which was highly associated with the use of mechanical ventilation.

BACKGROUND: Ceftazidime-avibactam (CAZ-AVI) is a combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam that is approved for the treatment of pediatric (≥ 3 months) and adult patients with complicated infections including hospital-acquired and ventilator-associated pneumonia (HAP/VAP), and bacteremia. This systematic literature review and meta-analysis (PROSPERO registration: CRD42022362856) aimed to provide a quantitative and qualitative synthesis to evaluate the effectiveness of CAZ-AVI in treating adult patients with bacteremia or nosocomial pneumonia caused by carbapenem-resistant Enterobacterales (non metallo-β-lactamase-producing strains) and multi-drug resistant (MDR) Pseudomonas aeruginosa infections.
METHODS: The databases included in the search, until November 7, 2022, were Embase and PubMed. A total of 24 studies (retrospective: 22, prospective: 2) with separate outcomes for patients with bacteremia or pneumonia were included.
RESULTS: The outcomes assessed were all-cause mortality, clinical cure, and microbiological cure. Qualitative (24 studies) and quantitative (8/24 studies) syntheses were performed. The quality of the studies was assessed using the MINORS checklist and the overall risk of bias was moderate to high.
CONCLUSIONS: In studies included in the meta-analysis, lower all-cause mortality for patients with bacteremia (OR = 0.30, 95% CI 0.19-0.46) and improved rates of clinical cure for patients with bacteremia (OR = 4.90, 95% CI 2.60-9.23) and nosocomial pneumonia (OR = 3.20, 95% CI 1.55-6.60) was observed in the CAZ-AVI group compared with the comparator group. Data provided here may be considered while using CAZ-AVI for the treatment of patients with difficult-to-treat infections.
BACKGROUND: PROSPERO CRD42022362856.

Objective Spinal fusions are gaining popularity as a means of treating spinal deformity and instability from a range of pathologies. The prevalence of glucocorticoid use has also increased in recent decades, and their systemic effects are well-documented. Although commonly used in the preoperative period, the effects of steroids on outcomes among patients undergoing spinal fusions are inadequately described. This study compares the odds of developing complications among patients who underwent single-level lumbar fusions with and without preoperative glucocorticoid use in hopes of establishing more evidence-based parameters for guiding preoperative steroid use. Methods The TriNetX multi-institutional electronic health record database was used to perform a retrospective, propensity score-matched analysis of clinical outcomes of two cohorts of patients who underwent posterior or posterolateral single-level lumbar fusions with and without interbody fusion, those who used glucocorticoids for at least one week within a year of fusion and those who did not. The outcomes of interest were examined within 30 days of the operation and included death, reoperation, deep or superficial surgical site infection (SSI), pneumonia, reintubation, ventilator dependence, tracheostomy, acute kidney injury (AKI), renal insufficiency, pulmonary embolism (PE) or deep venous thrombosis (DVT), urinary tract infection (UTI), emergency department (ED) visit, sepsis, and myocardial infarction (MI). Results The odds of developing pneumonia within 30 days of spinal fusion in the cohort that used glucocorticoids within one year of operation compared to the cohort without glucocorticoid use was 0.67 (p≤0.001, 95% CI: 0.59-0.69). The odds of requiring a tracheostomy within 30 days of spinal fusion in the cohort that used glucocorticoids within one year of operation compared to the cohort without glucocorticoid use was 0.39 (p≤0.001, 95% CI: 0.26-0.60). The odds of reoperation, deep and superficial SSI, and ED visits within 30 days of operation were significantly higher for the same glucocorticoid-receiving cohort, with odds ratios of 1.4 (p=0.003, 95% CI: 1.11-1.65), 1.86 (p≤0.001, 95% CI: 1.31-2.63), 2.28 (p≤0.001, 95% CI: 1.57-3.31), and 1.25 (p≤0.001, 95% CI: 1.17-1.33), respectively. After propensity score-matching, there was no significant difference between the odds of death, DVT, PE, MI, UTI, AKI, sepsis, reintubation, and ventilator dependence between the two cohorts. Conclusion In support of much of the current literature regarding preoperative glucocorticoid use and rates of complications, patients who underwent a single-level lumbar fusion and have used glucocorticoids for at least a week within a year of operation experienced significantly higher odds of reoperation, deep and superficial SSI, and ED visits. However, these patients using glucocorticoids were also found to have lower odds of developing pneumonia, renal insufficiency, and tracheostomy requirement than those who did not use steroids within a year of surgery.

BACKGROUND: Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP.
METHODS: We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events.
RESULTS: Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17-0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19-3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00-2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03-2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02-2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin.
CONCLUSIONS: This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria. Registration PROSPERO CRD42021226603.

Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP.
We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included.
We included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07-2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02-1.09], p = 0.002), PaO2/FiO2 ratio on the day of VAP (OR 0.997 [0.994-0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15-12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP.
ESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.

Non-ventilator associated hospital-acquired pneumonia (nvHAP) is a common nosocomial infection, but little is known about the outcomes of patients with nvHAP and the risk factors for adverse outcomes. In this retrospective study conducted in a Swiss tertiary care centre, adverse outcomes like in-hospital mortality, intensive care unit (ICU) admission, and mechanical ventilation, both all-cause and nvHAP-associated, were investigated. Of 244 patients with nvHAP, 72 (30%) died, 35 (14%) deaths were attributed to nvHAP. While 36 (15%) patients acquired nvHAP on the ICU, another 173 patients were eligible for ICU-transferral, and 76 (43.9%) needed ICU-admission. Of all patients hospitalized on the ICU 58 (51.8%) needed intubation due to nvHAP. Multivariable logistic regression analysis identified lower body mass index (OR per unit increase: 0.90, 95%CI: 0.82-0.98) and lower haemoglobin on admission (OR per unit in g/l increase: 0.98, 95%CI: 0.97-1.00) as patient specific factors independently associated with nvHAP-associated mortality. Given the frequency of nvHAP adverse outcomes, hospitals should evaluate increasing nvHAP prevention efforts, especially for patients at high risk for nvHAP mortality. To what extent pneumonia prevention interventions do lower nvHAP mortality in these patients is still to be evaluated.

OBJECTIVE: The incidences of nosocomial pneumonia in intensive care units (ICUs) in India have been reported to range from 9% to 58% and are associated with a mortality rate of 30-70%. Ceftazidime-avibactam has activity against OXA-48-like carbapenem-resistant Enterobacterales (CRE) and has a safer adverse effect profile as compared to the nephrotoxic colistin. The current study aimed to assess the effectiveness and usage pattern of ceftazidime-avibactam in gram-negative hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) in real-world settings in India.
METHODS: Electronic medical records of hospitalized patients in three prominent medical centers in India (Fortis Memorial Research Centre, Gurugram, S L Raheja Hospital, Mumbai, and Fortis Hospital, Anandapur, Kolkata) with nosocomial pneumonia and documented gram-negative Klebsiella pneumoniae (KP)-confirmed infection were collected. This study assessed the effectiveness, usage pattern of ceftazidime-avibactam, and clinical and microbiological cure rates.
RESULTS: Among the 116 patients included, 78.45% (91/116) showed clinical cure. Microbiological cure was observed in nine out of 13 (69.23%) patients. In the subset analysis, a clinical cure rate of 84.85% (28/33) and microbiological recovery rate of 62.50% (5/8) were observed when ceftazidime-avibactam was initiated within 72 hours of diagnosis. Ceftazidime-avibactam was administered for a mean (±SD) duration of 7.79 ± 4.43 days, with improvement in signs and symptoms reported among 91.38% (106/116). Ceftazidime-avibactam showed a susceptibility of 56% (28/56) in the study.
CONCLUSIONS: The current study showed a better clinical and microbiological cure rate with a safer tolerability profile of ceftazidime-avibactam in carbapenem-resistant KP nosocomial pneumonia and VAP. This study has further demonstrated that ceftazidime-avibactam may be used as one of the viable treatment choices in carbapenem-resistant KP with favorable clinical outcomes.

Pneumonia is a multifaceted illness with a wide range of clinical manifestations, degree of severity and multiple potential causing microorganisms. Despite the intensive research of recent decades, community-acquired pneumonia remains the third-highest cause of mortality in developed countries and the first due to infections; and hospital-acquired pneumonia is the main cause of death from nosocomial infection in critically ill patients. Guidelines for management of this disease are available world wide, but there are questions which generate controversy, and the latest advances make it difficult to stay them up to date. A multidisciplinary approach can overcome these limitations and can also aid to improve clinical results. Spanish medical societies involved in diagnosis and treatment of pneumonia have made a collaborative effort to actualize and integrate last expertise about this infection. The aim of this paper is to reflect this knowledge, communicated in Fifth Pneumonia Day in Spain. It reviews the most important questions about this disorder, such as microbiological diagnosis, advances in antibiotic and sequential therapy, management of beta-lactam allergic patient, preventive measures, management of unusual or multi-resistant microorganisms and adjuvant or advanced therapies in Intensive Care Unit.

OBJECTIVE: To evaluate the expression dynamics of biofilm genes in methicillin-resistant Staphylococcus aureus (MRSA) retrieved from endotracheal tubes (ETT) and to determine how gene regulation is attenuated in vitro where host-environmental factors are no longer present.
METHODS: Biofilm was grown (24 h) in tryptic broth soy plus 0.25% glucose for a clinical MRSA isolate in planktonic state and after sessile growth named ETT-MRSA (S2, S3, S4, S5, S6, S7). Gene expression of five biofilm-related genes (icaC, clfB, ebps, fnbB, and RNA III) was assessed consecutively from day 1 to day 4 after ETT growth through real-time PCR. 16S rRNA was used as a control.
RESULTS: The MRSA isolates retrieved from ETT were capable of producing biofilms dependent on ica. The gene expression dynamics of ETT-MRSA changed progressively compared to planktonic MRSA gene expression under both ambient air (p < 0.001) and ambient air with 5% CO2 (p < 0.001). Dynamic assessment of icaC expression in both atmospheric conditions showed progressive downregulation in vitro compared to in vivo ETT biofilms. The expression patterns of clfB and ebps genes were similar to icaC. In contrast, the expression of the RNA III gene showed progressive upregulation from day 1 to day 4 (p < 0.001).
CONCLUSIONS: MRSA loses its biofilm gene expression in vitro, by adaptive features across multiple generations, as evidenced by the progressive downregulation of icaC and upregulation of RNA III. These findings underscore the significance of host-environment dependence in regulating bacterial biofilm genes, highlighting its importance in diagnostics. Bacterial strains lose their host-specific characteristics as they are cultured in vitro.