Search Results (779)

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious respiratory problems. This review aims to provide a comprehensive overview of the pathophysiological mechanisms, diagnostic methods, and current therapeutic options for pneumonia caused by the SARS-CoV-2 virus. The pathophysiological process of severe pneumonia due to SARS-CoV-2 infection is characterized by direct lung damage from viral replication, an excessive immune system response, inflammation, impaired gas exchange, and multi-organ failure. The coexistence of various medical conditions leads to substantial lung impairment, resulting in hypoxia and respiratory failure, which can ultimately lead to fatal outcomes. The diagnosis of severe SARS-CoV-2 pneumonia is made through a combination of clinical, radiologic, and laboratory findings. A multifaceted approach integrating antiviral therapy, corticosteroids, oxygen supplementation, ventilatory management, and immunomodulation is imperative to control inflammation and enhance clinical outcomes. Early intervention, meticulous monitoring, and personalized care are paramount for enhancing survival and mitigating complications in critically ill patients with COVID-19 pneumonia. Full article

Introduction: The World Health Organization has declared carbapenem-resistant organisms a research and development priority. Although ceftazidime–avibactam was approved around a decade ago, there is still a lack of prospective data on the treatment of resistant pathogens with this agent. Methods: We conducted a prospective, observational, single-center, investigator-initiated study of patients treated with ceftazidime–avibactam for infections caused by carbapenem-resistant organisms. The primary outcome was clinical cure 14 days after the initiation of ceftazidime-avibactam treatment. Secondary outcomes, which were assessed on day 30, included microbiological failure, development of resistance, all-cause mortality, and length of stay in the intensive care unit. Results: A total of 50 patients were included in the study. At baseline, the median Charlson Comorbidity Index and Sequential Organ Failure Assessment Score were 5.5 and 7. Approximately three-quarters of the patients were treated in an intensive care unit and had undergone mechanical ventilation within the previous 7 days prior to the commencement of ceftazidime–avibactam treatment. Half of the patients were diagnosed with nosocomial pneumonia. Most infections were caused by Pseudomonas aeruginosa (48%) and Klebsiella pneumonia (28%). Clinical cure at day 14 was achieved in 59% of patients. Four deaths (9%) and two cases of microbiological failure (4%) were observed. The median length of stay in the intensive care unit was 14 days. There was no emergence of resistance to ceftazidime–avibactam. Discussion: Our study contributes to the growing body of evidence supporting the effectiveness of ceftazidime–avibactam in treating infections caused by carbapenem-resistant organisms. In this cohort of critically ill patients, our results in terms of both clinical success and survival are in the upper range compared to those from mainly retrospective and some prospective studies. Although the benefits of ceftazidime–avibactam have been demonstrated in this and other studies, it must be prescribed cautiously to ensure it remains effective. Full article

Infections with multidrug-resistant (MDR) organisms remain a significant cause of morbidity and mortality among liver transplant recipients, despite advances in surgical techniques and immunosuppressive therapy. This prospective observational study aimed to evaluate the impact of targeted perioperative antibiotic prophylaxis against MDR Gram-negative bacteria on postoperative infections and mortality in liver transplant recipients. Seventy-nine adult patients who underwent liver transplantation and were admitted to the ICU for more than 24 h postoperatively were included. Demographics, disease severity scores, comorbidities, and lengths of ICU and hospital stay were recorded. Colonization with carbapenem-resistant Gram-negative bacteria was assessed via preoperative and postoperative cultures from the blood, urine, rectum, and tracheal secretions. Patients were divided into two groups: those with MDR colonization or infection who received targeted prophylaxis and controls who received standard prophylaxis. Infectious complications (30.4%) occurred significantly less frequently than non-infectious ones (62.0%, p = 0.005). The most common infections were bacteremia (22.7%), pneumonia (17.7%), and surgical site infections (2.5%), with most events occurring within 15 days post-transplant. MDR pathogens isolated included Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Although overall complication and mortality rates at 30 days and 3 months did not differ significantly between groups, the targeted prophylaxis group had fewer infectious complications (22.8% vs. 68.5%, p = 0.008), particularly bacteremia (p = 0.007). Infection-related mortality was also significantly reduced in this group (p = 0.039). These findings suggest that identification of MDR colonization and administration of targeted perioperative antibiotics may reduce septic complications in liver transplant patients. Further prospective studies are warranted to confirm benefits on outcomes and resource utilization. Full article

Background/Objectives: The liver, the body’s primary detoxifying organ, is often affected by various inflammatory diseases, including hepatitis, cirrhosis, and non-alcoholic fatty liver disease (NAFLD), many of which can be exacerbated by secondary infections such as spontaneous bacterial peritonitis, bacteremia, and sepsis—particularly in patients with advanced liver dysfunction. The global rise in these conditions underscores the need for effective interventions. Natural products have attracted attention for their potential to support liver health, particularly through synergistic combinations of plant extracts. Epavin, a dietary supplement from Erbenobili S.r.l., formulated with plant extracts like Taraxacum officinale (L.), Silybum marianum (L.) Gaertn., and Cynara scolymus (L.), known for their liver-supporting properties, has been proposed as adjuvant for liver functions. The aim of this work was to evaluate of Epavin’s antioxidant, anti-inflammatory, and protective effects against heavy metal-induced toxicity. In addition, the antibacterial effect of Epavin against a panel of bacterial strains responsible for infections associated with liver injuries has been evaluated. Methods: The protection against oxidative stress induced by H₂O₂ was evaluated in HepG2 and BALB/3T3 cells using the dichlorofluorescein diacetate (DCFH-DA) assay. Its anti-inflammatory activity was investigated by measuring the reduction in nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages using the Griess assay. Additionally, the cytoprotecting of Epavin against heavy metal-induced toxicity and oxidative stress were evaluated in HepG2 cells using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] (MTT) and DCFH-DA assays. The antibacterial activity of Epavin was assessed by determining the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) against Gram-positive (Enterococcus faecalis ATCC 29212, and BS, Staphylococcus aureus 25923, 29213, 43300, and BS) and Gram-negative (Escherichia coli 25922, and BS, Klebsiella pneumoniae 13883, 70063, and BS) bacterial strains using the microdilution method in broth, following the Clinical and Laboratory Standards Institute’s (CLSI) guidelines. Results: Epavin effectively reduced oxidative stress in HepG2 and BALB/3T3 cells and decreased NO production in LPS-stimulated RAW 264.7 macrophages. Moreover, Epavin demonstrated a protective effect against heavy metal-induced toxicity and oxidative damage in HepG2 cells. Finally, it exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 1.5 to 6.0 mg/mL. Conclusions: The interesting results obtained suggest that Epavin may serve as a valuable natural adjuvant for liver health by enhancing detoxification processes, reducing inflammation, and exerting antibacterial effects that could be beneficial in the context of liver-associated infections. Full article

Background and Objectives: COVID-19 may have long-term adverse effects on bone health, particularly in individuals aged ≥50 years with obesity or diabetes, who are predisposed to impaired bone quality. Materials and Methods: This retrospective cohort study used TriNetX data from 141 healthcare organizations across North America and Western Europe. Patients aged ≥50 years with overweight (body mass index 25–30 kg/m²), obesity (body mass index ≥ 30 kg/m²), or type 2 diabetes (T2DM) and COVID-19 (2019–2024) were propensity score-matched to non-COVID-19 controls. Exclusion criteria included prior overweight, obesity, diabetes, osteoporosis, T-score ≤ −2.5, Z score ≤ −2.0, fractures, pneumonia, tuberculosis, and cancer. Outcomes included new-onset osteoporosis, fragility fractures, and low T-scores (≤−2.5). Cox regression estimated hazard ratios (HRs); sensitivity analyses assessed lag effects (1–4 years). Results: Among 327,933 matched pairs, COVID-19 was linked to increased osteoporosis risk at 3 years (HR, 1.039; 95% CI, 1.003–1.077) and 6 years (HR, 1.095; 95% CI, 1.059–1.133). Sensitivity analysis showed rising risk with longer lag times: HRs were 1.212, 1.379, 1.563, and 1.884 at 1 to 4 years, respectively. Subgroup analyses confirmed consistent trends. Conclusions: COVID-19 is independently associated with elevated long-term osteoporosis risk in older adults with new-onset overweight, obesity, or T2DM, peaking at 4 years post-infection and persisting through 6 years. Full article

Background: Combining direct disk diffusion (DD) testing with antimicrobial stewardship (AMS) may optimize antibiotic use and improve outcomes in patients with Gram-negative bloodstream infections (GNBSIs). Methods: This quasi-experimental study was conducted at Srinagarind Hospital, Khon Kaen University, between 13 September 2022 and 11 April 2023. Patients with GNBSIs were enrolled during two phases: a standard care phase (13 September 2022–2 January 2023) and an intervention phase (16 January 2023–11 April 2023), during which therapy adjustments were guided by DD results interpreted by infectious disease specialists. Results: Among the 141 patients included (68 in the standard care group and 73 in the intervention group), the mean age was 61.7 years, and 60.2% were male. Escherichia coli (36.5%) and Klebsiella pneumoniae (27.6%) were the most frequently isolated pathogens, with intra-abdominal and urinary tract infections being the most common sources. Multidrug-resistant (MDR) organisms were identified in 48.9% of cases. Compared to standard care, the intervention group had a significantly shorter median time to optimal therapy (40.0 vs. 59.1 h, p = 0.037) and a higher proportion of patients receiving optimal therapy within 72 h (86.2% vs. 62.3%, p = 0.002). While 30-day mortality did not differ significantly between groups (17.2% vs. 16.7%, p = 0.98), MDR bacteremia and ICU admission were associated with increased mortality. In contrast, receiving optimal therapy within 72 h was associated with reduced mortality. Conclusion: Direct DD testing combined with AMS significantly reduced the time to optimal antibiotic therapy and decreased inappropriate antibiotic use in GNBSI patients. Achieving optimal therapy within 72 h was associated with a trend toward reduced mortality. Full article

Necropsies are commonly used to diagnose the causes of death in feedyard cattle, but the documentation of multiple organ system involvement and concurrent lesions is limited. This observational study aimed to determine the frequency of such findings and their associations with animal demographics. Systemic necropsies were conducted for 889 cattle mortalities with minimal autolysis across six feedyards in the Central High Plains during the summers of 2022 and 2023. Lesions and abnormalities were recorded along with arrival weight, sex, days on feed (DOFs), and number of treatments. The results showed that 72% of mortalities had more than one gross lesion, averaging 2.3 lesions per animal. The most common organ systems affected together were digestive and pulmonary (19%), followed by cardiovascular, digestive, and pulmonary (6%), and cardiovascular and pulmonary (5%). Common concurrent lesions included bronchopneumonia with an interstitial pattern (BIP) and gastrointestinal lesions (GI) (8%), bronchopneumonia and GI (7%), and acute interstitial pneumonia (AIP) and GI (3%). A generalized linear mixed effects model revealed that the likelihood of multiple lesions increased with DOFs (p = 0.02). These findings highlight the value of thorough necropsy documentation to enhance our understanding of disease and guide improved feedyard management and treatment practices. Full article

Adrenomedullin (AM) is a bioactive peptide that is strongly induced during severe inflammation, including pneumonia and sepsis, and serves as an organ-protective factor. The plasma concentration of AM is markedly increased in the novel coronavirus disease COVID-19 and is closely related to the severity of the disease and prognosis of patients. We performed two investigator-initiated trials to evaluate the efficacy and safety of AM in patients with moderate-to-severe COVID-19. This multicenter, double-blind, placebo-controlled phase-2a trial evaluated COVID-19 patients with severe (n = 33) and moderate (n = 31) pneumonia in Japan. Patients were randomly assigned to receive either 15 ng/kg/min AM or placebo. The primary endpoint was the duration of mechanical ventilation (MV) for severe pneumonia and oxygen support for moderate pneumonia. The main secondary endpoint was clinical status up to 30 days after the intervention. No differences in primary or secondary endpoints were observed between the AM and placebo groups in patients with severe or moderate pneumonia. In the severe pneumonia group, three patients in the placebo group died due to respiratory failure, and one patient in the AM group died due to respiratory failure. The respiratory function test at 30 days in the moderate pneumonia group tended to be better than that in the AM group and approached significance (p = 0.073). Although mild adverse events caused by the vasodilatory effects of AM were noted, the safety of AM for treating pneumonia was confirmed. In these trials, we did not observe a definitive efficacy of AM in moderate to severe pneumonia. Alternative strategies for the treatment of AM in pneumonia require further research. Full article

Acinetobacter baumannii is listed by the World Health Organization as an emerging bacterial priority pathogen, the prevalence and multidrug resistance of which have been increasing. This functional genomics study aimed to understand the drug-resistance mechanisms of an extensively drug-resistant (XDR) A. baumannii strain (IRMCBCU95U) isolated from a transtracheal aspirate sample from a female patient with end-stage renal disease in Saudi Arabia. The whole genome of IRMCBCU95U (4.3 Mbp) was sequenced using Oxford Nanopore long-read sequencing to identify and compare the antibiotic-resistance profile and genomic features of A. baumannii IRMCBCU95U. The antibiogram of A. baumannii IRMCBCU95U revealed resistance to multiple antibiotics, including cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem and piperacillin/tazobactam. A comparative genomic analysis between IRMCBCU95U and A. baumannii K09-14 and ATCC 19606 identified significant genetic heterogeneity and mosaicism among the strains. This analysis also demonstrated the hybrid nature of the genome of IRMCBCU95U and indicates that horizontal gene transfer may have occurred between these strains. The IRMCBCU95U genome has a diverse range of genes associated with antimicrobial resistance and mobile genetic elements (ISAba1 and IS26) associated with the spread of multidrug resistance. The presence of virulence-associated genes that are linked to iron acquisition, motility and transcriptional regulation confirmed that IRMCBCU95U is a priority human pathogen. The plasmid fragment IncFIB(pNDM-Mar) observed in the strain is homologous to the plasmid in Klebsiella pneumoniae (439 bp; similarity: 99.09%), which supports its antimicrobial resistance. From these observations, it can be concluded that the clinical A. baumannii IRMCBCU95U isolate is an emerging extensively drug-resistant human pathogen with a novel combination of resistance genes and a plasmid fragment. The complex resistome of IRMCBCU95U highlights the urgent need for genomic surveillance in hospital settings in Saudi Arabia to fight against the spread of extensively drug-resistant A. baumannii. Full article

Objectives: Carbapenem-resistant Gram-negative bacteria (CR-GNB) infections in intensive care units (ICUs) are increasingly prevalent and associated with high mortality. This study aimed to investigate the distribution of isolated bacteria and determine the factors associated with mortality among ICU patients diagnosed with CR-GNB infections. Methods: This retrospective study included 95 patients admitted to the ICU between February 2022 and July 2024 who were diagnosed with CR-GNB infections via culture and initiated on treatment. Thirty-day mortality was defined as the clinical outcome, and patients were divided into two groups: survivors (Group 1, n = 42) and deceased (Group 2, n = 53). Demographic, clinical, laboratory, and microbiological data were analyzed. Results: Advanced age, the presence of malignancy, an elevated Charlson Comorbidity Index (CCI), lower platelet counts, and higher C-reactive protein (CRP) levels were significantly associated with mortality (p < 0.05). Trauma-related admissions were more common among survivors, while sepsis-related admissions predominated among non-survivors. No statistically significant associations were observed between antibiotic regimen type and mortality. Culture-based pathogen distribution revealed A. baumannii as the predominant organism in respiratory samples, while K. pneumoniae was more frequently isolated from bloodstream and urinary specimens. Conclusions: Mortality in ICU patients with CR-GNB infections is influenced by both baseline comorbidities and infection-related inflammatory markers. This study provides region-specific insights from a high-resistance ICU setting and may inform risk stratification, prognostication, and management strategies in critically ill patients with CR-GNB infections. Full article

Background and Objectives: Immune checkpoint inhibitors (ICIs) have emerged as groundbreaking agents in cancer therapy; however, their immune-related adverse effects, especially pulmonary toxicity, significantly limit their use. This study aimed to determine the incidence and risk factors associated with ICI-induced pulmonary toxicity. Materials and Methods: We conducted a prospective observational study involving 126 patients aged ≥18 years with malignancies treated with ICIs between April 2022 and April 2024. Patients were followed every six months over a two-year period. Clinical, laboratory, and radiological data were collected to assess pulmonary toxicity. Results: The mean age of our patients was 62.93 ± 12.94 years, and 81% were male. The ICI-related pulmonary toxicity rate was 16.7%, and the all-cause mortality rate was 68.3%. In the analysis, the conditions associated with pulmonary toxicity were the type of malignancy, the presence of lung cancer, COPD, long-term ICI use, dyspnea, cough and sputum, the pre-ICI lung nodule mass, and high blood monocyte levels. Our regression analysis results for the determination of risk factors showed a 7.70-fold increase in the presence of cough symptoms, a 4.57-fold increase in the presence of COPD, a 0.998-fold increase for every 1 unit decrease in lymphocyte count, and an 11.75-fold increase in risk for a monocyte count of 130 or less. Conclusions: Our study’s findings suggest that patients with identifiable risk factors for pulmonary toxicity should undergo closer monitoring and early diagnostic evaluation during ICI therapy to reduce morbidity and mortality. Full article

Respiratory syncytial virus (RSV) represents one of the main respiratory infections found among immunocompromised patients. Objective: The study analyzes the incidence of RSV infection in different populations of immunocompromised patients as organ transplant recipients (lung, other solid organs, hematopoietic stem cells) and oncologic patients (solid organ malignancy and hematological malignancy) compared to a group of non-immunocompromised patients. We also assessed the prevalence of viral, bacterial, and mycotic coinfection. Moreover, we aimed at evaluating the efficacy of ribavirin treatment in terms of mortality reduction. Methods: We conducted a retrospective analysis on a total of 466 transplant patients undergoing bronchoscopy with bronchoalveolar lavage for suspected viral disease or surveillance between 2016 and 2023, compared to 460 controls. Results: The incidence of RSV was significantly higher in immunocompromised patients, particularly in those with lung and bone marrow transplants. Among RSV+ patients, a higher prevalence of viral (influenza virus), bacterial (S. pneumoniae, M. pneumoniae, Nocardia spp.), and fungal (Aspergillus spp.) coinfections were observed. The efficacy of ribavirin in reducing mortality did not show significant differences compared to supportive therapy alone. Conclusions: The results of our exploratory study suggest that immunocompromised patients are particularly vulnerable to RSV infection and coinfections. Our hypothesis-generating data warrant the need for future studies aimed at exploring preventive and therapeutic strategies for RSV infection in these high-risk patient groups. Full article

Many rural communities in Malawi use groundwater from boreholes and shallow wells for drinking and cooking with limited or no treatment because it is considered as a safe source of water. The contamination of groundwater sources by antimicrobial resistant bacteria renders the water unsafe to use. This study investigated the antibiotic susceptibility of pathogenic micro-organisms isolated from groundwater sources in T/A Makhwira, Chikwawa. Water samples were collected from 13 boreholes and 7 protected shallow wells from T/A Makhwira, Chikwawa. E. coli, Salmonella enterica ssp. Arizona, K. pneumoniae, ESBL E. coli, and ESBL K. pneumoniae were detected in some water samples. Antibiotic susceptibility tests showed that the isolates had a high resistance to Ampicillin (42%), followed by Trimethoprim-sulfamethoxazole (26%), Ciprofloxacin (21%), Doxycycline, and Amoxicillin/clavulanic acid (16%). The isolates had a very high sensitivity to Gentamicin (89%). The study revealed that the water from some boreholes and shallow wells in T/A Makhwira is highly contaminated and needs to be treated before consumption. Drinking untreated water from these sources could transfer antibiotic-resistant bacteria to humans because the groundwater may act as a vehicle for the transmission of these antibiotic-resistant bacteria. Full article

Klebsiella pneumoniae is a Gram-negative, encapsulated bacterium recognized by the World Health Organization (WHO) as a critical priority for new therapeutic strategies due to its increasing multidrug resistance (MDR). Antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative to antibiotics, exhibiting a broad spectrum of action and multiple molecular targets, and has been proposed for the treatment of clinically relevant infections such as pneumonia. However, despite excellent in vitro photodynamic inactivation outcomes, the success of in vivo therapy still faces challenges, particularly due to the presence of lung surfactant (LS) in the alveoli. LS entraps photosensitizers, preventing these molecules from reaching microbial targets. This study investigated the potential of indocyanine green (ICG) in combination with the biocompatible polymer Gantrez™ AN-139 for the photoinactivation of K. pneumoniae. Initial in vitro experiments demonstrated that aPDT with ICG alone is effective against K. pneumoniae in a concentration- and light dose-dependent manner, achieving total eradication at 75 µg/mL of ICG and 150 J/cm² of 808 nm light. When aPDT was performed with similar parameters in the presence of LS, no bacterial killing was observed. However, a significant synergistic effect was observed when ICG (25 µg/mL) was combined with a low concentration of Gantrez™ AN-139 (0.5% m/v) in the presence of dipalmitoylphosphatidylcholine (DPPC), the main component of LS. This formulation resulted in a substantial reduction (3.6 log₁₀) in K. pneumoniae viability. These findings highlight the potential of Gantrez™ AN-139 as an efficient carrier to enhance the efficacy of ICG-mediated aPDT against K. pneumoniae, even in the presence of lung surfactant, a necessary step before the in vivo experiments. Full article