Search Results (58)

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

Background/Objectives: Gram-negative bloodstream infections (GN-BSIs) in the critically ill carry significant mortality, which is exacerbated by delays in appropriate therapy. To improve the time to effective therapy, aminoglycosides are often recommended as empiric adjunctive antimicrobials. However, there is a paucity of clinical data supporting this practice. This study’s objective was to evaluate the safety and efficacy of adjunctive aminoglycosides compared to β-lactam monotherapy in patients admitted to the intensive care unit (ICU) with GN-BSI. Methods: This was a retrospective, propensity-matched cohort study of critically ill patients with GN-BSI. The primary outcome was 15-day all-cause mortality. The secondary endpoints evaluated included 30-day mortality, ICU-free survival days, 60-day relapse, 30-day readmission, development of acute kidney injury (AKI), and new resistance. Results: A total of 209 propensity-matched patients were included for analysis: 136 received β-lactam monotherapy and 73 received adjunctive aminoglycoside. The primary outcome of 15-day all-cause mortality was not significantly different between groups (17% vs. 21%; p = 0.644). Additional secondary endpoints of 30-day mortality (22% vs. 25%), ICU-free survival (12.1 vs. 12.2 days), 60-day relapse (3.3% vs. 7.4%), and 30-day readmission (23% vs. 18%) did not yield significant differences. The proportion of AKI was higher in the adjunctive aminoglycoside group but was not found to be significantly different (26.5% vs. 37%). Conclusions: The use of adjunctive aminoglycosides for GN-BSI did not affect clinical outcomes in the critically ill. Full article

Background: The optimal duration of antibiotic treatment for extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) bloodstream infections (BSI) in intensive care unit (ICU) is not established. We aim to evaluate the frequency and clinical outcomesof a short appropriate antibiotic treatment (≤7 days) (SAT) for ESBL-E BSI acquired in the ICU. We specifically assessed the rate of ESBL-E BSI relapse, and in-ICU mortality. Method: All patients who acquired ESBL-E BSI in three ICU in Northern France between January 2011 and June 2022 were included in a multicenter retrospective cohort study. The factors associated with prescribing short (SAT, ≤7 days) versus long (LAT, >7 days) antibiotic treatment were analyzed. To evaluate the impact of SAT on mortality in the ICU, an estimation was applied using a Cox model with a time-dependent co-variable adjusted by inverse weighting of the propensity score. Results: In total, 379 patients were included. The proportion of patients receiving a SAT was 40% in the entire cohort and 25% in survivors beyond 7 days. In bivariate analysis, the factors associated with prescribing a SAT in survivors were shorter pre-bacteremia ICU stay (p = 0.005), lower proportion of chronic renal failure history (p = 0.034), cancer (p = 0.042), or transplantation (p = 0.025), less frequent exposure to carbapenem within 3 months (p = 0.015). There was a higher proportion of septic shock (p = 0.017) or bacteremia secondary to pneumonia (p = 0.003) in the group of survivors receiving a LAT. After adjustment, no difference in survival was found between the two groups (HR: 1.65, 95%CI: 0.91–3.00, p = 0.10). Conclusion: In our cohort, one quarter of patients with ESBL-E bacteremia acquired in the ICU surviving beyond 7 days were treated with a SAT. SAT did not appear to affect survival. Patients who could benefit from a SAT need to be better identified. Full article

Patients with hematological malignancies (HMs) are at higher risk of severe COVID-19 and secondary infections, which further complicate their outcomes. This study evaluated the impact of secondary infections (SIs) on mortality in hospitalized HM patients with SARS-CoV-2 infection and identified risk factors associated with SIs. We included 217 patients with HMs and COVID-19 admitted to a tertiary hospital in Rome, from April 2020 to September 2022. SIs occurred in 44.2% of patients, with bloodstream infections (42.7%) and respiratory infections (30.5%) being most frequent; among the latter, COVID-19-associated pulmonary aspergillosis (CAPA) was observed in 41.4% of cases. Viral reactivations, predominantly CMV, occurred in 9.2% of patients. The overall mortality rate was 29%, with higher mortality observed in patients with SIs (47.4% vs. 14.7%, p < 0.01). Risk factors for SIs included severe COVID-19 (OR = 2.957, p < 0.05) and prolonged hospitalization (OR = 1.095, p < 0.001). Severe COVID-19 (OR = 8.229, p < 0.001), intensive care unit (ICU) admission (OR = 15.232, p < 0.001), chronic steroid therapy (OR = 2.803, p < 0.05), SIs (OR = 2.892, p < 0.05), and viral reactivation (OR = 6.269, p < 0.01) were independent predictors of mortality. SIs and viral reactivations are common in patients with HMs and SARS-CoV-2 infection and significantly increase mortality, highlighting the need for timely management and preventive strategies in this vulnerable population. Full article

Background/Objectives: Uncertainty persists about the best methods and timing for providing medical nutrition therapy (MNT) in the acute phase of critical illness. We conducted an overview of systematic reviews to examine and appraise the findings of the current systematic reviews and performed an updated meta-analysis incorporating newly published randomized controlled trials (RCTs) to investigate whether enteral nutrition (EN) is superior to the combination of EN and parenteral nutrition (PN) in patients admitted to the intensive care unit (ICU). Methods: We systematically searched three databases to retrieve systematic reviews and RCTs. Two independent reviewers performed the screening, data extraction, and quality assessment processes. The random effects model was utilized to synthesize the data regarding primary and secondary outcomes. Results: There was no difference between the two interventions regarding the efficacy and safety endpoints, apart from the bloodstream infections, which were found to be increased in the group that received the combination of EN+PN (RR = 1.27, 95%CI = 1.03 to 1.56, PI = 0.91 to 1.77, I² = 0%). Conclusions: According to the present overview of systematic reviews and meta-analyses, there was no observed benefit on mortality, length of ICU stay or hospitalization, and duration of mechanical ventilation in critically ill patients receiving a combination of EN and PN in comparison to those receiving sole enteral nutrition in the ICU. Furthermore, no difference was observed in the rates of respiratory infections as well as the appearance of adverse events, such as vomiting and diarrhea. On the other hand, there was an increase in bloodstream infection rates in patients who received EN+PN compared to EN alone. Due to the limited implications of the results in clinical practice, further research is needed. Full article

To assess the clinical usefulness of teicoplanin optimized by means of a therapeutic drug monitoring (TDM)-guided approach for treating secondary bloodstream infections (BSIs) caused by Enterococcus faecium. Hospitalized patients having in the period 1 March 2021–31 October 2024 a documented BSI caused by glycopeptide-susceptible Enterococcus faecium being treated with teicoplanin as definitive targeted therapy optimized by means of a real-time TDM-guided expert clinical pharmacological advice (ECPA) program were retrospectively included. Teicoplanin trough concentrations (C_min) ranging from 20 to 30 mg/L were defined as the desired target of efficacy based on international guidelines. Univariate analysis was performed for assessing variables potentially associated with microbiological failure (defined as persistence at the infection site of the index Enterococcus faecium strain after more than 7 days from starting treatment as documented by follow-up blood cultures). Overall, 67 patients (median age 70 years; male 55.2%) were included. Catheter-related BSIs (50.7%) and intrabdominal/biliary tract (29.9%) infections were the main sources of Enterococcus faecium BSI. The desired target of teicoplanin C_min was attained in 62.7% of patients at the first TDM assessment and significantly increased to 85.1% (p = 0.003) at subsequent TDM-guided ECPA instances during the overall treatment course. Microbiological eradication was obtained in 95% of cases (63/67). In the univariate analysis, failing effective source control was the only variable associated with an increased risk of microbiological failure (75.0% vs. 12.7%; p = 0.01). Targeted TDM-guided teicoplanin therapy, coupled with effective source control of the primary infection site by granting microbiological eradication in the vast majority of cases, may be considered a reasonable strategy for managing glycopeptide-susceptible Enterococcus faecium secondary BSIs. Full article

Background: Nutritional support is crucial in critically ill patients to enhance recovery, reduce infections, and improve outcomes. This meta-analysis compared early enteral nutrition (EEN) and early parenteral nutrition (EPN) to evaluate their efficacy in adult critically ill patients. Methods: A systematic review of 14 studies involving 7618 patients was conducted, including randomized controlled trials, prospective cohorts, and retrospective analyses. The primary outcomes were mortality and infectious complications, while secondary outcomes included intensive care unit length of stay (ICU-LOS), hospital length of stay (H-LOS), mechanical ventilation days, and gastrointestinal (GI) complications. Results: The results showed no significant difference in mortality between EEN and EPN (OR 1.03, 95% CI 0.93–1.14). EEN reduced bloodstream infections (OR 0.73, 95% CI 0.57–0.93), ICU-LOS (MD −0.18 days, 95% CI −0.33 to −0.04), and H-LOS (MD −1.15 days, 95% CI −1.38 to −0.93). However, EEN was associated with higher GI complications, such as vomiting and diarrhea (OR 2.25, 95% CI 1.97–2.58), while mechanical ventilation days showed no significant difference. Conclusions: These findings support prioritizing EEN in critically ill patients with functional gastrointestinal systems to improve infection control and recovery while emphasizing the importance of careful monitoring to mitigate gastrointestinal complications. Full article

G-quadruplexes (G4s) are non-canonical secondary structures that play a crucial role in the regulation of genetic expression. This study explores the interaction between G4s and a small family of oligostyrylbenzene (OSB) derivatives, characterized by tris(styryl)benzene and tetrastyrylbenzene backbones, functionalized with either trimethylammonium or 1-methylpyridinium groups. Initially identified as DNA ligands, these OSB derivatives have now been recognized as potent G4 binders, surpassing in binding affinity commercially available ligands such as pyridostatin and displaying good selectivity for G4s over duplex DNA. Furthermore, OSB derivatives 1 and 2 demonstrated significant antiparasitic activity against bloodstream forms of T. brucei and extracellular L. major, with high selectivity indices when compared to MRC-5 healthy control cells. Derivatives 1 and 2 exhibited moderate biocidal effects against a range of Gram-positive and Gram-negative bacterial strains. Notably, a synergistic antibacterial effect was observed when these compounds were combined with traditional antibiotics, particularly against Acinetobacter baumannii, highlighting their potential utility in addressing drug-resistant bacterial infections. The differences in bioactivity among the OSB derivatives can be attributed to variations in cellular uptake, as proved by flow cytometry analysis. This suggests that the degree of cellular internalization plays a pivotal role in the observed antiparasitic and antibacterial efficacy. Full article

Introduction: Daptomycin (DAP) is a cyclic lipopeptide that exhibits potent in vitro activity against many drug-resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Despite substantial reports evaluating the clinical outcomes of DAP within the adult population, real-world data are lacking in children. The primary goal of this evaluation was to describe the clinical characteristics and outcomes of DAP use in pediatric patients across a wide range of infections. Methods: This retrospective evaluation included patients < 18 years of age who were treated with DAP from January 2014 to May 2023. The primary objective was to evaluate the composite clinical success, which was defined as a 30-day survival, the lack of a 30-day microbiological recurrence, and the resolution of signs and symptoms of an acute infection without therapy modifications based on clinical failures. Secondary objectives included adverse effects potentially attributable to DAP and reasons for DAP utilization. Results: Forty patients were included, which were predominately male (62.5%) and white (52.5%), with a median age of 8.7 [IQR, 4.4–16.0] years. DAP was used for a wide range of infections, including central line-associated bloodstream infections (CLABSIs; 32.5%), infective endocarditis (15.0%), surgical-site infections (12.5%), and osteomyelitis (12.5%). The most common pathogen isolated was MRSA (37.5%), and most patients were bacteremic (60.0%). The median DAP dose was 8 [IQR, 6–10] mg/kg, and the median duration of the DAP therapy was 11.5 [IQR, 4.8–18.8] days. Most patients achieved composite clinical success (75.0%). An adverse effect occurred in 5.0% of the patients. DAP was prescribed the most for its ease of use/ability to facilitate discharge (40.0%) and/or for issues with alternative therapies (37.5%). Conclusion: Most pediatric patients that received DAP demonstrated clinical success with a low incidence of adverse effects. Larger, real-world studies of DAP use are necessary to further assess clinical outcomes. Full article

Bloodstream infections (BSIs) can be primary or secondary, with significant associated morbidity and mortality. Primary bloodstream infections (BSIs) are defined as infections where no clear infection source is identified, while secondary BSIs originate from a localized infection site. This study aims to compare patterns, outcomes, and medical costs between primary and secondary BSIs and identify associated factors. Conducted at the University Hospital of Patras, Greece, from May 2016 to May 2018, this single-center retrospective cohort study included 201 patients with confirmed BSIs based on positive blood cultures. Data on patient characteristics, clinical outcomes, hospitalization costs, and laboratory parameters were analyzed using appropriate statistical methods. Primary BSIs occurred in 22.89% (46 patients), while secondary BSIs occurred in 77.11% (155 patients). Primary BSI patients were younger and predominantly nosocomial, whereas secondary BSI was mostly community-acquired. Clinical severity scores (SOFA, APACHE II, SAPS, and qPitt) were significantly higher in primary compared to secondary BSI. The median hospital stay was longer for primary BSI (21 vs. 12 days, p < 0.001). Although not statistically significant, mortality rates were higher in primary BSI (43.24% vs. 26.09%). Total care costs were significantly higher for primary BSI (EUR 4388.3 vs. EUR 2530.25, p = 0.016), driven by longer hospital stays and increased antibiotic costs. This study underscores the distinct clinical and economic challenges of primary versus secondary BSI and emphasizes the need for prompt diagnosis and tailored antimicrobial therapy. Further research should focus on developing specific management guidelines for primary BSI and exploring interventions to reduce BSI burden across healthcare settings. Full article

The optimal doses of ceftazidime–avibactam (CZA) and ceftolozane–tazobactam (C/T) for treating multidrug-resistant (MDR) Pseudomonas aeruginosa (PSA) in patients utilizing renal replacement therapy (RRT) are not well established. Hence, the objective of this study is to evaluate the clinical outcomes associated with the suggested doses of CZA and C/T in patients with PSA infection utilizing RRT. Methods: This is a retrospective study conducted at our hospital between September 2018 and March 2022. Clinical cure was the primary endpoint, while microbiologic cure, 30-day recurrence, and 30-day mortality were the secondary endpoints. Results: In total, 45 subjects met the inclusion criteria, with 25 receiving CZA and 20 receiving C/T. The median age was 69 (52–81) and 69 (61.5–83) years, respectively, while the median weight was 70 (55.5–81.5) and 66 (57–79) kg, respectively. Clinical cure was achieved in 12 (48%) subjects in the CZA group and 12 (60%) in the C/T group (p = 0.432). Of the 36 subjects who had repeated cultures, a microbiologic cure was achieved in 14/23 (60%) subjects and 10/13 (76.9%) subjects (p = 0.273). Thirty-day recurrence was reported in 3 (12%) cases in the CZA group and 6 (30%) in the C/T group (p = 0.082). The 30-day mortality was 13 (52%) subjects in the CZA group and 10 (50%) in the C/T group (p = 0.894). The median maintenance dose of CZA was 1.88 (0.94–3.75) g and 2.25 (1.5–2.25) g for C/T. Multivariate logistic regression analysis indicated that both drugs did not differ significantly in clinical cure. Bloodstream infection (BSI) (OR = 25, 95% CI: 1.63–411.7, p = 0.021) was the only independent factor associated with clinical cure in this population. Conclusions: Our findings indicated that C/T and CZA did not significantly differ in achieving clinical cure in patients with MDR PSA infections undergoing RRT. Larger clinical trials are needed to confirm our findings. Full article

During the pandemic of COVID-19, the rates of bloodstream infection associated with venous catheter in patients infected with the disease admitted to an intensive care unit rose significantly. In this study, we evaluated the occurrence of bloodstream infections in patients with SARS-CoV-2 and the variables that made the patients more susceptible to the catheter-associated bloodstream infection (CABSI). Blood culture results from patients interned between March 2020 and December 2021 (n= 109) were collected electronically from the hospital information system and then analyzed. The following variables presented statistical relevance after an adjusted model as follows: obesity (p = 0.003) and time of use of catheter before infection (p = 0.019). In conclusion, patients with shorter catheter use time and obesity had higher incidence of CABSI. Full article

Dermacoccus barathri is the first reported pathogen within the Dermacoccus genus to cause a catheter-related bloodstream infection, which occurred in 2015. In this study, the complete genome assembly of Dermacoccus barathri was constructed, and the complete genome of Dermacoccus barathri FBCC-B549 consists of a single chromosome (3,137,745 bp) without plasmids. The constructed genome of D. barathri was compared with those of two closely related species within the Dermacoccus genus. D. barathri exhibited a pattern similar to Dermacoccus abyssi in terms of gene clusters and synteny analysis. Contrary to previous studies, biosynthetic gene cluster (BGC) analysis for predicting secondary metabolites revealed the presence of the LAP biosynthesis pathway in the complete genome of D. barathri, predicting the potential synthesis of the secondary metabolite plantazolicin. Furthermore, an analysis to investigate the potential pathogenicity of D. barathri did not reveal any antibiotic resistance genes; however, nine virulence factors were identified in the Virulence Factor Database (VFDB). According to these matching results in the VFDB, despite identifying a few factors involved in biofilm formation, further research is required to determine the actual impact of D. barathri on pathogenicity. The complete genome of D. barathri is expected to serve as a valuable resource for future studies on D. barathri, which currently lack sufficient genomic sequence information. Full article

Antimicrobial resistance is a global healthcare threat with significant clinical and economic consequences peaking at secondary and tertiary care hospitals where multidrug-resistant Gram-negative bacteria (MDR GNB) lead to poor outcomes. A prospective study was conducted between January and December 2019 for all invasive bloodstream infections (BSIs) secondary to MDR GNB in Qatar identified during routine microbiological service to examine their clinical, microbiological, and genomic characteristics. Out of 3238 episodes of GNB BSIs, the prevalence of MDR GNB was 13% (429/3238). The predominant MDR pathogens were Escherichia coli (62.7%), Klebsiella pneumoniae (20.4%), Salmonella species (6.6%), and Pseudomonas aeruginosa (5.3%), while out of 245 clinically evaluated patients, the majority were adult males, with the elderly constituting almost one-third of the cohort and with highest observed risk for prolonged hospital stays. The risk factors identified included multiple comorbidities, recent healthcare contact, previous antimicrobial therapy, and admission to critical care. The in-hospital mortality rate was recorded at 25.7%, associated with multiple comorbidities, admission to critical care, and the acquisition of MDR Pseudomonas aeruginosa. Resistant pathogens demonstrated high levels of antimicrobial resistance but noticeable susceptibility to amikacin and carbapenems. Genomic analysis revealed that Escherichia coli ST131 and Salmonella enterica ST1 were the predominant clones not observed with other pathogens. Full article

(1) Background: The advantage of using carbapenems over beta-lactam/beta-lactamase inhibitor combinations in critically ill septic patients still remains a debated issue. We aimed to assess the comparative impact of an optimized pharmacokinetic/pharmacodynamic (PK/PD) target attainment of piperacillin-tazobactam vs. meropenem on the trend over time of both Sequential Organ Failure Assessment (SOFA) score and inflammatory biomarkers in critically ill patients receiving continuous infusion (CI) monotherapy with piperacillin-tazobactam or meropenem for treating documented Gram-negative bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP). (2) Methods: We performed a retrospective observational study comparing critically ill patients receiving targeted treatment with CI meropenem monotherapy for documented Gram-negative BSIs or VAP with a historical cohort of critical patients receiving CI piperacillin-tazobactam monotherapy. Patients included in the two groups were admitted to the general and post-transplant intensive care unit in the period July 2021–September 2023 and fulfilled the same inclusion criteria. The delta values of the SOFA score between the baseline of meropenem or piperacillin-tazobactam treatment and those at 48-h (delta 48-h SOFA score) or at 7-days (delta 7-days SOFA) were selected as primary outcomes. Delta 48-h and 7-days C-reactive protein (CRP) and procalcitonin (PCT), microbiological eradication, resistance occurrence, clinical cure, multi-drug resistant colonization at 90-day, ICU, and 30-day mortality rate were selected as secondary outcomes. Univariate analysis comparing primary and secondary outcomes between critically ill patients receiving CI monotherapy with piperacillin-tazobactam vs. meropenem was carried out. (3) Results: Overall, 32 critically ill patients receiving CI meropenem monotherapy were compared with a historical cohort of 43 cases receiving CI piperacillin-tazobactam monotherapy. No significant differences in terms of demographics and clinical features emerged at baseline between the two groups. Optimal PK/PD target was attained in 83.7% and 100.0% of patients receiving piperacillin-tazobactam and meropenem, respectively. No significant differences were observed between groups in terms of median values of delta 48-h SOFA (0 points vs. 1 point; p = 0.89) and median delta 7-days SOFA (2 points vs. 1 point; p = 0.43). Similarly, no significant differences were found between patients receiving piperacillin-tazobactam vs. meropenem for any of the secondary outcomes. (4) Conclusion: Our findings may support the contention that in critically ill patients with documented Gram-negative BSIs and/or VAP, the decreases in the SOFA score and in the inflammatory biomarkers serum levels achievable with CI piperacillin-tazobactam monotherapy at 48-h and at 7-days may be of similar extent and as effective as to those achievable with CI meropenem monotherapy provided that optimization on real-time by means of a TDM-based expert clinical pharmacological advice program is granted. Full article