Search Results (117)

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: 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

Klebsiella pneumoniae is a major public health concern due to its role in Gram-negative bacteremia, which leads to high mortality and increased healthcare costs. This study characterizes phenotypic and genomic features of K. pneumoniae isolates from clinical samples in Karachi, Pakistan. Among 507 isolates, 213 (42%) were carbapenem-resistant based on disk diffusion and MIC testing. Urine (29.7%) and blood (28.3%) were the most common sources, with infections predominantly affecting males (64.7%) and individuals aged 50–70 years. Colistin was the only antibiotic showing consistent activity against these isolates. The whole-genome sequencing of 24 carbapenem-resistant K. pneumoniae (CR-KP) isolates revealed bla_NDM-5 (45.8%) as the dominant carbapenemase gene, followed by bla_NDM-1 (12.5%) and bla_OXA-232 (54.2%). Other detected bla_OXA variants included bla_OXA-1, bla_OXA-4, bla_OXA-10, and bla_OXA-18. The predominant beta-lactamase gene was bla_CTX-M-15 (91.6%), followed by bla_CTX-M-163, bla_CTX-M-186, and bla_CTX-M-194. Sequence types ST147, ST231, ST29, and ST11 were associated with resistance. Plasmid profiling revealed IncR (61.5%), IncL (15.4%), and IncC (7.7%) as common plasmid types. Importantly, resistance was driven not only by acquired genes but also by chromosomal mutations. Porin mutations in OmpK36 and OmpK37 (e.g., P170M, I128M, N230G, A217S) reduced drug influx, while acrR and ramR mutations (e.g., P161R, G164A, P157*) led to efflux pump overexpression, enhancing resistance to fluoroquinolones and tigecycline. These findings highlight a complex resistance landscape driven by diverse carbapenemases and ESBLs, underlining the urgent need for robust antimicrobial stewardship and surveillance strategies. Full article

The utility of follow-up blood cultures (FUBCs) in Gram-negative bloodstream infections (GN-BSIs) remains controversial. The lack of randomized controlled trials and guidelines has led to the inappropriate use of unnecessary FUBCs, increasing costs, the length of hospital stays, and antibiotic use. In this review, we aim to evaluate the strengths and limitations of the most significant studies on FUBCs in GN-BSIs, proposing a more personalized approach for using FUBCs in GN-BSIs. FUBCs seem to have a low yield of persistent positive BC in uncomplicated GN-BSIs and no effect on mortality, but some selected patients may benefit. Available studies show different results regarding the mortality and benefit of FUBCs, mainly due to differences in methodology and patient characteristics. However, selected patients with endovascular infections, central venous catheters, unfavorable responses, and no source control seem to benefit the most. Randomized controlled trials are warranted in order to confirm these indications. Full article

The growing problem of infections due to pathogens with antimicrobial resistance, especially Gram-negative bacteria, has led to the development of new β-lactam/β-lactamase inhibitor combination antibiotics. During the last 2 years from the writing of this article, cefepime/enmetazobactam, aztreonam/avibactam, and sulbactam/durlobactam were approved for use in clinical practice. Cefepime/enmetazobactam targets extended-spectrum β-lactamase (ESBL)-producing Pseudomonas aeruginosa and Enterobacterales. It is indicated for the treatment of patients with complicated urinary tract infections, including pyelonephritis, in Europe and the USA, and also for hospital-acquired pneumonia, ventilator-associated pneumonia, and bacteremia associated with those infections (only in Europe). The antimicrobial spectrum of aztreonam/avibactam includes carbapenem-resistant Enterobacterales. Aztreonam/avibactam is indicated for the treatment of adult patients who suffer from complicated intra-abdominal infections, complicated urinary tract infections including pyelonephritis, hospital-acquired pneumonia, and ventilator-associated pneumonia due to aerobic Gram-negative infections with limited therapeutic options. Sulbactam/durlobactam, a combination of 2 β-lactamase inhibitors, is indicated for the treatment of adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to the Acinetobacter baumannii–calcoaceticus complex [including carbapenem-resistant Acinetobacter baumannii (CRAB) infections]. Full article

Background and Clinical Significance: Klebisella variicola belongs to the Klebsiella pneumoniae complex. It is a Gram-negative, facultative anaerobic, and nonmotile bacillus, mainly isolated in plants. However, as an emerging human pathogen, it has been isolated in immunocompromised patients with urinary tract infections, pneumonia, and bacteremia. K. variicola infection in pregnancy, responsible for acute chorioamnionitis, has never been reported. Case Presentation: We present a case of a twin pregnancy at 17 + 5 weeks in which chorioamnionitis and fetal inflammatory responses such as funisitis and chorionic vasculitis were due to an ascending infection of K. variicola. The pathogen was isolated postmortem in fetal blood and tissues and the placenta using MALDI-ToF mass spectrometry (MALDI-ToF MS). The accuracy of this microbiological diagnosis sheds further light on the epidemiology and virulence of K. variicola in the prenatal setting. Conclusions: In the case of miscarriage, microbiological investigations on the fetus should always be recommended to identify the exact microorganism in order to target the medical treatment and manage subsequent pregnancies. Full article

Cefiderocol is a novel cephalosporin antibiotic approved for urinary tract infections and hospital-acquired or ventilator-associated pneumonias caused by difficult-to-treat Gram-negative pathogens. To date, its use in treating difficult-to-treat Gram-negative infections in burn patients has been minimally described in the literature. Our aim was to evaluate cefiderocol use in a population of burn patients initiated on cefiderocol for resistant Gram-negative infections. A retrospective chart review of nine patients was conducted. Two patients were treated for pneumonia; five for bacteremia, three of which had coexisting burn wound infections or pneumonia; one was treated for a burn wound infection alone; and one patient was treated for a simultaneous burn wound infection, pneumonia, and bacteremia. The pathogens treated included the following: multidrug-resistant Pseudomonas aeruginosa, carbapenem-resistant Acinetobacter baumannii, and carbapenem-resistant Enterobacterales. Three isolates were confirmed as New Delhi metallo-beta-lactamase (NDM) producers, though this was likely an underestimate as genetic testing is not routinely performed at our institution and not all the isolates were tested. One of the nine patients in this study succumbed to their infection. Of note, the multidrug-resistant Pseudomonas aeruginosa in this patient tested intermediate to cefiderocol. The patients were treated with cefiderocol for a median of 14 days, most commonly in combination with other antimicrobial therapies. Treatment with cefiderocol appeared to be efficacious in this population of burn patients when other antibiotics routinely used for complicated infections caused by multidrug-resistant (MDR) Gram-negative pathogens showed treatment failure or resistance. Full article

Background: Psychrobacter species are aerobic, Gram-negative, spherical-to-rod-shaped, psychrophilic bacteria that belong to the Moraxellaceae family. In spite of their uncommon manifestation in the general population, infections due to Psychrobacter spp. are increasingly identified especially in immunocompromised individuals or patients with severe comorbidities. Objectives: This review aims to analyze all reported instances of Psychrobacter spp. infections in humans, with an emphasis on data pertaining to epidemiology, microbiology, antimicrobial resistance, treatment strategies, and mortality outcomes. Methods: A narrative review was performed through a literature search of PubMed/MedLine and Scopus databases. Results: In total, 12 articles offered data on 12 patients infected with Psychrobacter spp. Their mean age was 33.41 years, while 63.64% of them were male. Immunosuppression was the predominant risk factor (33.3%). Bacteremia was the most commonly observed type of infection (41.6%), followed by meningitis, skin infection, and conjunctivitis. Psychrobacter immobilis was the most usually identified species (33.3%). The pathogen exhibited sensitivity to most antimicrobials. The most widely administered antimicrobials included cephalosporins (70%), followed by aminopenicillins and vancomycin (40%, respectively). The clinical outcome depended primarily on the infection site; mortality rate was high (44.4%), especially in cases of bacteremia (50%). Conclusion: Due to the potential of Psychrobacter spp. to cause serious infection, clinicians and laboratory professionals should consider it in the differential diagnosis in patients with infections by Gram-negative spherical bacteria, particularly in patients with significant comorbidities and immunodeficiency, in order to accurately establish the diagnosis and proceed to the right treatment. Full article

Gram-negative bacteria possess an asymmetric outer membrane, where the outer leaflet consists of LPSs and the inner leaflet comprises phospholipids. Cronobacter sakazakii, an opportunistic milk-borne pathogen that causes severe neonatal meningitis and bacteremia, displays diverse lipopolysaccharide (LPS) structures. As a barrier of the bacterial cell, LPSs likely influenced C. sakazakii resistance to environment stresses; however, there are no research reports on this aspect, hindering the development of novel bactericidal strategies overcoming the pathogen’s resilience. In the present study, therefore, C. sakazakii BAA894 and two LPS mutants (ΔlpxM and ΔwaaC) were employed to investigate its influences. The ΔwaaC mutant showed lower resistance to acidic, alkali, oxidative, and osmotic stresses compared to the wild-type strain BAA894, and the ΔlpxM mutant exhibited lower desiccation resistance but higher osmotic resistance. To uncover potential reasons for these differences, comparative lipidomics was conducted. The results showed that compared to BAA894, both mutants showed drastic changes in lipid quantity, and many changed lipids were unsaturated. Additionally, eleven lipid classes exhibited significant variation in the relative content. In particular, the polyunsaturated TGs with double bonds at 5, 7, 12, and 14 displayed significant variation between the wild type and two mutants. Our study is the first to reveal that the changes in the LPS structure of C. sakazakii resulted in altered lipid profiles and intensities, which may be a critical biochemical basis for bacterial resistance to harsh stresses. Full article

Background/Objectives: Pandoraea species are Gram-negative, aerobic, rod-shaped bacteria that belong to the Burkholderiaceae family and the Betaproteobacteria class. Despite their rare occurrence in the general population, they have been increasingly observed as the causes of infection in immunocompromised individuals or patients with severe comorbidities. The present review seeks to examine all documented cases of Pandoraea spp. infections in humans, focusing on data related to epidemiology, microbiology, antimicrobial susceptibility, treatment options, and mortality rates. Methods: A systematic review was conducted through a literature search of the PubMed/MedLine and Scopus databases. This review is subjected to certain limitations regarding the data accuracy or pathogen identification molecular techniques applied in the studies. Results: In total, 29 studies provided information on 43 patients with Pandoraea spp. infections. The mean age of the patients was 42 years, and 58% were male. Cystic fibrosis was these patients’ most prevalent risk factor (39.5%). The most frequently reported types of infection were lower respiratory tract infections (74.41%) and bacteremia (30.23%), followed by infective endocarditis, pancreatitis, upper respiratory tract infection, and osteomyelitis (4.65%). P. apista was the most regularly isolated species (37.2%), while antimicrobial resistance was lower for carbapenems, especially for imipenem (17.14%). The most commonly administered antibiotics included carbapenems (82%), cephalosporins, and trimethoprim/sulfamethoxazole (35.89%). The infection outcome primarily depended on the type of infection; mortality rates were high (30.23%) and particularly elevated for bloodstream infections. The protocol for this review was registered in Prospero (ID: CRD42024579385). Conclusions: Due to Pandoraea’s unique antimicrobial resistance pattern and capacity to induce severe infection, clinicians should include it when making a differential diagnosis, especially in patients with severe comorbidities and immunodeficiency. Full article

Background: Antipseudomonal β-lactams (APBL) are commonly used for empirical therapy of Gram-negative bloodstream infections (BSI). This retrospective cohort study examines risk factors for prolonged APBL use (≥48 h) in patients with Enterobacterales BSI and compares 28-day mortality between early de-escalation of APBL and prolonged APBL therapy. Methods: Adult patients admitted to two community hospitals in South Carolina with Enterobacterales BSI from January 2010 to June 2015 were included in this study. Data were extracted manually from medical records. Multivariate logistic regression and Cox proportional hazards analyses were used to examine predictors of prolonged APBL therapy and mortality, respectively. Results: Among 993 patients with Enterobacterales BSI, 491 (49%) underwent early de-escalation of APBL and 502 (51%) received prolonged APBL therapy. Cancer, immune compromised status, residence at a skilled nursing facility, a high Pitt bacteremia score, non-urinary source of infection, and BSI due to AmpC-producing Enterobacterales were independently associated with prolonged use of APBL. Antimicrobial stewardship interventions were inversely associated with prolonged APBL use. Early de-escalation of APBL was not associated with increased mortality. Conclusions: This study exemplifies the safety and effectiveness of early de-escalation of APBL in Enterobacterales BSI. Antimicrobial stewardship strategies should be implemented to encourage the practice of early de-escalation of antimicrobial therapy, including in high-risk populations. Full article

The epidemiology of bacteremia and the antibiotic resistance profile (ARP) of Gram-negative bacilli (GNB) in hematological malignancies (HM) and hematopoietic stem cell transplant (HSCT) patients may differ according to geographic region. In addition, multidrug-resistant organisms (MDROs) may impact mortality. This is a prospective, observational, and multicenter study. The first episodes of bacteremia in adult patients with HM or HSCT were included. The risk factors for 30-day mortality were identified. One thousand two hundred and seventy-seven episodes were included (HM: 920; HSCT: 357). GNB were isolated in 60.3% of episodes, with Enterobacterales (46.9%) and P. aeruginosa (8.5%) being the most frequent. Gram-positive cocci were isolated in 41.9% of episodes, with coagulase-negative staphylococci (19.8%) and S. aureus (10.4%) being the most frequent. MDROs were isolated in 40.2% (24.4% GNB). The ARP of GNB in patients with HM vs. HSCT was cefepime: 36.8% vs. 45.7% (p = 0.026); piperacillin–tazobactam: 31.05% vs. 45.2% (p < 0.0001); carbapenems: 18.9% vs. 27.3% (p = 0.012); and aminoglycosides: 9.3% vs. 15.4% (p = 0.017), respectively. Overall mortality between patients with HM and HSCT was 17.5% vs. 17.6% (p = 0.951), respectively. The risk factors for mortality were relapsed and refractory underlying disease, corticosteroids use, respiratory source, septic shock, and GNB resistant to meropenem, while 7-day clinical response was a protective factor for survival. Bacteremia was frequently caused by GNB, with a large proportion of MDROs and a high level of antibiotic resistance, especially in patients with HSCT. Carbapenem-resistant GNB bacteremia was associated with a significant increase in mortality. Full article

Bacillus sp. G2112, an isolate from cucumber plants that inhibited plant pathogens, produces not only surfactins, iturins, and fengycins common to many Bacillus spp., but also a large variety of N-acyl-(depsi)peptides related to A-3302-B and nobilamides. Four known and fourteen previously unreported nobilamide peptides were characterized using high-resolution mass spectrometry, tandem mass spectrometry, and NMR. The stereochemistry of the amino acids of nobilamide peptides was determined using Marfey’s method. The diversity of nobilamide peptides from Bacillus sp. G2112 resulted from the incorporation of different acyl groups and amino acids in the sequence. The peptides occur in linear or cyclic form. In addition, a truncated N-acetylpentapeptide was produced. Agar diffusion assays with selected nobilamide peptides against plant pathogens and human pathogens revealed that A-3302-B and its N-acyl homologs, A-3302-A and nobilamide J, exhibited powerful antibiotic activity (at 5 µg/hole) against Lysinibacillus sphaericus that can cause severe sepsis and bacteremia in patients. Moreover, nobilamide peptides from Bacillus sp. G2112 strongly promoted biofilm formation in the Gram-positive Mycobacterium aurum and Gram-negative pseudomonads. Structurally diverse nobilamides from Bacillus sp. G2112, whether linear or cyclic, penta and heptapeptides, induced biofilm formation, suggesting that the common N-acetyl-D-Phe-D-Leu-L-Phe-D-allo-Thr-L-Val amino acid sequence motif is important for the biofilm-inducing activity. Full article

Bloodstream infection is one of the most important and increasing complications in patients with severe burns. Most of the species affecting this population are Gram-negative bacilli that exhibit antimicrobial resistance. We conducted this study to determine the antimicrobial susceptibility profile and resistance mechanisms of these bacterial infections and their clinical associations on morbidity and mortality. We analyzed a retrospective cohort of burn patients. All patients included in this study had monobacterial blood stream infections during their hospital stay. We performed phenotypic and genotypic tests to determine the antimicrobial resistance mechanism and profile of each strain. Univariate and multivariate logistic regression analysis was performed between variables. We found 109 patients with monobacterial bacteremia. Pseudomonas spp. (50.7%), A. baumannii (46.4%), and Klebsiella spp. (13.8%) were the most common causative microorganisms. The Pseudomonas spp. isolates showed resistance to imipenem (81.5%), mainly by class A and class B carbapenemases. The A. baumannii isolates conferred resistance to imipenem (56.2%), mainly by class D carbapenemases. One quarter of Klebsiella spp. showed resistance to 3rd generation cephalosporins. We also observed that a total body surface area greater than 40% and three or more different types of invasive procedures might be related to increased mortality. Multidrug resistance is highly present. The extent of the burned area and a high number of different types of invasive procedures had an impact in decreasing survivorship in burn patients with bacteremia. Full article