Search Results (240)

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

Aim: Antibiotic de-escalation (ADE) is essential, but appears to be underperformed although being possible, which we refer to as a ‘missed opportunity’. We aimed to analyze the ADE missed opportunities in Gram-negative bloodstream infections (BSIs) in a setting with a high antimicrobial resistance profile. Methods: A retrospective, two-centered cohort study was performed from 1 January 2018 to 30 June 2019, including adults with mono- or polymicrobial Gram-negative BSIs. All ADE episodes and 30-day mortality were noted. Results/Discussion: Out of 273 BSIs (43 ADE vs. 230 no-ADE episodes), 101 were considered a ‘missed’ opportunity of ADE (36.9%, 101/273). In multivariate analysis, ADE opportunities were missed 4.4 times more (OR = 4.4; 95% CI 1.24–15.9) in the presence of hematological malignancy and 6.2 times more (OR = 6.2; 95% CI 1.76–22.2) in ESBL. Contrary to this, ADE opportunities were missed 0.24 times less (OR = 0.24; 95% CI 0.09–0.61) among patients with E. coli BSIs, and 0.17 less (OR = 0.17; 95% CI 0.05–0.67) if ertapenem was used as an empirical agent. The ADE missed opportunity group had a higher mortality rate, which is statistically significant in univariate analysis, but not in multivariate analysis. Conclusion: The presence of ESBL and hematological malignancy were the significant barriers to appropriate ADE practice in our study. A good stewardship program must address physician hesitation in ADE practice. Full article

Background/Objective: This study aimed to evaluate the effectiveness of very early oral transition in Enterobacterales bloodstream infections (E-BSIs), identify factors associated with it, compare the effectiveness of different oral options, and assess its economic and ecological benefits. Methods: Retrospective, observational cohort study including monomicrobial E-BSI in clinically stable adult patients by day 3 of bacteremia with oral antibiotic options. Transition to oral antibiotics by day 3 or earlier (early oral (EO) group) was compared to later transition or remaining on intravenous therapy (nEO group). Early oral transition-associated factors were analyzed. Oral high-dose beta-lactams (BLs) were compared to quinolones (QLs) or trimethoprim/sulfamethoxazole (TS). Economic and ecological costs were assessed. Results: Of 345 E-BSI, 163 (47.2%) were in the EO group, characterized by more urinary tract infections (UTIs) and shorter hospital stays. The nEO group had higher Charlson Comorbidity Index (CCI), extended-spectrum beta-lactamase (ESBL) production, greater source control need, and longer time to clinical stability. There were no significant differences in mortality and relapse. UTIs were associated with early oral transition (OR 2.02, IC 95% 1.18–3.48), while higher CCI (0.85, 0.77–0.95), source control need (0.39, 0.19–0.85), longer time to clinical stability (0.51, 0.39–0.66), and ESBL isolates (0.39, 0.19–0.80) hindered this practice. High-dose BLs and QL/TS were equally effective. Early oral transition resulted in 38.794 KgCO₂eq reduction and EUR 269,557.99 savings. Conclusions: Very early oral transition at day 3 or before in stable E-BSI patients is effective, eco-sustainable, and cost-effective; UTI is related with the early oral switch, while comorbidities, ESBL production, source control need, or longer time to clinical stability hinder this practice. Full article

Determining the optimal duration of antibiotic therapy for infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) is a critical challenge in clinical medicine, balancing therapeutic efficacy against the risks of adverse effects and antimicrobial resistance. This narrative review synthesises current evidence and guidelines regarding antibiotic duration for MDR-GNB infections, emphasising bloodstream infections (BSI), hospital-acquired and ventilator-associated pneumonia (HAP/VAP), complicated urinary tract infections (cUTIs), and intra-abdominal infections (IAIs). Despite robust evidence supporting shorter courses (3–7 days) in uncomplicated infections caused by more susceptible pathogens, data guiding optimal therapy duration for MDR-GNB remain limited, particularly concerning carbapenem-resistant Enterobacterales (CRE), difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), and carbapenem-resistant Acinetobacter baumannii (CRAB). Current guidelines from major societies, including IDSA and ESCMID, provide explicit antimicrobial selection advice but notably lack detailed recommendations on the duration of therapy. Existing studies demonstrate non-inferiority of shorter versus longer antibiotic courses in specific clinical contexts but frequently exclude critically ill patients or those infected with non-fermenting MDR pathogens. Individualised duration decisions must integrate clinical response, patient immunologic status, infection severity, source control adequacy, and pharmacologic considerations. Significant knowledge gaps persist, underscoring the urgent need for targeted research, particularly randomised controlled trials assessing optimal antibiotic duration for the most challenging MDR-GNB infections. Clinicians must navigate considerable uncertainty, relying on nuanced judgement and close monitoring to achieve successful outcomes while advancing antimicrobial stewardship goals. Full article

Objectives: There is a scarcity of studies on multisite infections (MSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). The primary objectives of this research were to determine the clinical characteristics of CRKP MSI, and the risk factors of infection and mortality. Methods: Patients with a CRKP bloodstream infection (BSI) were enrolled retrospectively between January 2017 and December 2021 in Xijing Hospital, China. The risk factors for CRKP MSI and mortality were evaluated. The demographic data, clinical and microbiological characteristics, therapy and outcomes were analyzed. Results: Among 101 patients, 74.3% (75/101) had a diagnosis of CRKP MSI, while 25.7% (26/101) of CRKP non-MSI. The overall case fatality rate was 42.6% (43/101). Multivariate analysis indicated that previous surgery (OR 3.971, 95% CI 1.504–10.480, p = 0.005) and ICU admission (OR 3.322, 95% CI 1.252–8.816, p = 0.016) were independent risk factors for CRKP MSI. ICU admission (OR 4.765, 95% CI 1.192–19.054, p = 0.027), a Pitt bacteremia score (PBS) > 4 (OR 3.820, 95% CI 1.218–11.983, p = 0.022) and thrombocytopenia (OR 8.650, 95% CI 2.573–29.007, p < 0.001) were independent risk factors for mortality due to CRKP MSI. Conclusions: Our findings confirmed that CRKP MSIs were associated with poorer outcomes. To improve prognosis, early screening of individuals at the highest risk is vital. Full article

Bloodstream infections (BSIs) are a major cause of morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. Staphylococcus epidermidis, typically a skin commensal, is increasingly recognized as a pathogen in these vulnerable individuals. This study investigated whether genomic differences exist between infectious and gastrointestinal colonizing S. epidermidis isolates from AML patients and how these compare to colonizing and infectious isolates from other patient groups and biogeographic sites. We analyzed 114 isolates—44 from AML patients (23 infections, 21 GI colonizers) and 70 from public datasets (34 infections, 36 colonizers). Stool samples underwent 16S rRNA sequencing and culture to identify colonization, while bloodstream isolates were sequenced and compared. Genomic profiling using Roary, Scoary, Phyre2, and InterProScan revealed that infectious and GI-colonizing AML isolates were phylogenetically close but genomically distinct. Infectious isolates from AML patients were significantly enriched for resistance genes (e.g., mecA, mecR1, mecI, ANT(4′)-Ib) and the biofilm-associated gene icaA. AML infectious isolates harbored more resistance genes and mobile elements than non-AML strains but lacked widespread classical virulence factors. These results suggest that S. epidermidis pathogenicity in immunocompromised hosts is driven by genomic adaptability and antibiotic tolerance rather than traditional virulence mechanisms. Full article

Background: Bloodstream infections (BSIs) caused by multidrug-resistant non-fermenting Gram-negative bacilli, particularly Pseudomonas aeruginosa and Acinetobacter baumannii, represent a growing public health concern, especially in tertiary care settings. This study aimed to describe the epidemiological and antimicrobial resistance trends of P. aeruginosa and A. baumannii isolated from blood cultures over an eight-year period (2017–2024) at a tertiary infectious disease hospital in Bucharest, Romania, especially in the context of the disruption caused by the SARS-CoV-2 pandemic. Methods: A retrospective study was conducted on 43,951 blood cultures processed at the National Institute of Infectious Diseases. Species identification and antibiotic susceptibility testing (AST) were performed using VITEK2, MALDI-TOF MS, and supplementary phenotypic methods. AST interpretation followed EUCAST guidelines. Results: Out of all of the positive blood cultures, 112 (3.63%) were P. aeruginosa and 158 (5.12%) A. baumannii. Multidrug-resistance (MDR) was identified in 46% of P. aeruginosa and 90.73% of A. baumannii isolates. Resistance trends varied, with P. aeruginosa showing a decrease in MDR rates post-COVID-19 pandemic and following antimicrobial stewardship implementation. In contrast, A. baumannii displayed persistently high resistance, with carbapenem and aminoglycoside resistance rates reaching 100% by 2024. Colistin resistance, though low overall, increased in the latter years. Conclusions: The findings highlight the dynamic nature of antimicrobial resistance among P. aeruginosa and A. baumannii. Effective infection control and antimicrobial stewardship programs are crucial in curbing the rise of MDR strains, particularly amid healthcare system disruptions such as the COVID-19 pandemic. Full article

Background: In vitro synergy testing (ST) is a useful means to gauge the performance ofantibiotic combinations against multidrug-resistant (MDR) Gram-negative bacteria (GNB). This study aimed to determine synergy of antibiotics against paediatric bloodstream (BS) carbapenem-resistant Enterobacterales (CRE) and extremely drug-resistant (XDR) Acinetobacter species. Methods: This cross-sectional study was conducted at a public tertiary hospital in South Africa, from January 2023 to December 2023. Sixty-eight isolates from children with bloodstream infections (BSI), comprising 55.9% (38/68) CRE and 44.1% (30/68) XDR Acinetobacter species, were performed ST using the fixed-ratio Epsilometer-test method. Combinations of colistin and meropenem, colistin and fosfomycin, colistin and tigecycline, meropenem and fosfomycin, meropenem and tigecycline, and fosfomycin and tigecycline were tested. Results: In vitro synergy for CRE was best demonstrated with tigecycline and meropenem, at 92.1% (35/38), and fosfomycin and meropenem at 73.7% (28/38). Among the XDR Acinetobacter species, the highest rates of synergy of 76.7% (23/30) were observed with tigecycline and meropenem. The absence of synergy was noted with colistin and meropenem for the CRE, with many displaying indifference and antagonism at rates of 65.8% and 22%. Most XDR Acinetobacter species (56.7%; 17/30) expressed indifference to colistin and meropenem with synergy and antagonism displayed in 23.3% and 10% of isolates. Conclusions: This study highlights tigecycline and meropenem displaying impressive in vitro synergy when compared to the in-use colistin and meropenem for CRE and XDR Acinetobacter species. Tigecycline and meropenem may be a viable salvage therapeutic option for MDR Gram-negative paediatric infections. Future research is warranted to confirm in vivo synergy clinically. 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

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

In small animal practice, blood cultures (BCs) are essential for diagnosing bacterial bloodstream infections (BSIs) and guiding targeted antimicrobial therapy, particularly in relation to the rise of multidrug-resistant (MDR) pathogens. This study analyzed 96 positive BCs from dogs and cats at the Veterinary University Hospital (VUH) of Bologna (2020–2024), assessing bacterial prevalence, antimicrobial resistance, and associated risk factors. Escherichia coli was the most common isolate (29/96), followed by Streptococcus canis (11/96). MDR percentage was 29.2% (28/96), with Gram-negatives associated with higher rates (p = 0.040). Nearly half of the cases (46.9%, 45/96) were suspected healthcare-associated infections (HAIs) significantly associated with the number of invasive devices used (p = 0.008) and with the absence of co-positive samples (p = 0.012). Empirical antibiotic therapy was administered in 94.8% (91/96) of cases, with ampicillin–sulbactam and marbofloxacin as the most used drugs. In vitro empirical therapy appropriateness was 76.9% (70/91). MDR was associated with inappropriate empirical therapy (p < 0.001). Mortality within 30 days was 36.5% (35/96), significantly linked to antibiotic escalation (p = 0.006). The findings highlight the need for systematic BC surveillance in veterinary settings to optimize treatment strategies (especially in countries with restrictions on antibiotic use in animals) to mitigate MDR spread and to protect public health. Full article

Background: Bloodstream infections (BSIs) are both a primary cause and a severe complication of hospitalization. This retrospective study aims to analyze the epidemiology of BSIs at the University Hospital of Palermo from 2018 to 2024. Methods: We conducted a single-center, retrospective, observational study at the University Hospital Paolo Giaccone in Palermo, analyzing microbiological data from blood cultures collected between 1 January 2018 and 31 December 2024. Results: A total of 6345 blood culture isolates from 2967 patients were analyzed. Bacteremia-related mortality per 1000 patients rose from 5.1% in 2018 to 10.5% in 2024. The most isolated pathogens were non-aureus staphylococci (39.7%), followed by Klebsiella pneumoniae (12.1%) and Staphylococcus aureus (7.47%). Acinetobacter baumannii and Pseudomonas aeruginosa were more prevalent in ICUs. The number of K. pneumoniae, A. baumannii, S. aureus, and P. aeruginosa isolates per 1000 admitted patients increased significantly over time. Oxacillin resistance in S. aureus peaked at 49.0% in 2020 before declining, while among non-aureus staphylococci, it remained consistently high (>80%). Carbapenem-resistant K. pneumoniae peaked at 80% in 2022 before decreasing in 2024. Resistance to ceftazidime-avibactam and meropenem-vaborbactam was observed in 11.3% and 11.8% of K. pneumoniae, respectively. Multivariable analysis identified A. baumannii and K. pneumoniae BSIs as independent predictors of in-hospital mortality. Additionally, female sex, pneumonia, and central nervous system infections were significant risk factors for mortality. Conclusions: We observed an increasing trend in overall bacteremia-related mortality from 2018 to 2024. Microbiological data highlight the predominance of non-aureus staphylococci, K. pneumoniae, and S. aureus as leading pathogens of BSI, with A. baumannii emerging as a significant threat, particularly in ICUs. Rising antimicrobial resistance, especially among K. pneumoniae, underscores the urgent need for robust antimicrobial stewardship programs. K. pneumoniae and A. baumannii were associated with higher mortality. Full article

Rapid identification and antimicrobial susceptibility testing are essential for timely bloodstream infection (BSI) management. This study aimed to investigate the performance and turnaround time of multiple rapid diagnostic methods in a microbiology laboratory without 24/7 operation. This study included 236 positive blood culture bottles. Rapid identification methods were assessed with the SepsiTyper kit and the FilmArray blood culture identification 2 (BCID2) panel. Rapid antimicrobial susceptibility testing (AST) methods involved direct AST using the BD Phoenix M50 system and QuantaMatrix direct and rapid antimicrobial susceptibility testing (dRAST) and resistance gene detection with the FilmArray BCID2 panel. Conventional methods were used to compare results. The turnaround time was analyzed from blood culture positivity to preparation initiation and from preparation initiation to result reporting. Both rapid identification methods significantly reduced the turnaround time (~1 day and 19 h) compared to conventional identification. SepsiTyper demonstrated higher species-level accuracy in monomicrobial samples, whereas BCID2 outperformed in polymicrobial cases. Among the rapid AST methods, BCID2 and dRAST enabled result reporting within 24 h of positivity. Preparation delays were >45% of the overall turnaround time. Rapid diagnostics substantially shortened the BSI diagnostic time, even in limited-operation settings. Their clinical utility may be improved through 24/7 laboratory workflows. Full article

Background: Data from African neonatal units conducting bloodstream infection (BSI) surveillance is limited. Methods: Prospective clinical and laboratory surveillance of incident BSI episodes was conducted among in-patients at the 132-bed neonatal service at Tygerberg Hospital, Cape Town, South Africa (2017–2021), describing patient demographics, BSI rates, pathogen profiles, and empiric antibiotic concordance rates. Results: In total, 842 BSI episodes were identified in 740 neonates; most were preterm (661/740; 89.3%) and of low birth weight (640/740; 86.5%). The early onset BSI rate (<3 days of life) was 2.9/1000 live births, with S. agalactiae, K. pneumoniae, and E. coli predominating. Over time, ampicillin plus gentamicin coverage rates for early onset BSI pathogens declined from 93.8% to 63.6%. The healthcare-associated BSI rate (onset >3 days of life) was 3.4/1000 in-patient days, with K. pneumoniae, S. aureus, and S. marcescens predominating. Antibiotic coverage rates for healthcare-associated BSIs improved over time, from 72.2% to 89.2% (piperacillin plus amikacin) and from 68.1% to 84.6% (meropenem). Nearly one-third of BSI episodes were fatal (244/842; 29.0%), with two-thirds of these deaths considered BSI-attributable. Gram-negative BSIs increased mortality (OR 2.88; 95% CI 1.93–4.32) compared to Gram-positive BSIs (p < 0.001). Discordant empiric antibiotic therapy (OR 1.55; 95% CI 1.10–2.17) increased the risk of death compared to concordant therapy (p = 0.012). Conclusions: Neonatal BSI surveillance demonstrated that Gram-negative pathogens remain important causes of early onset and healthcare-associated BSIs in this resource-limited neonatal service. Declining coverage rates for empiric antibiotics prescribed for early onset BSI highlight the need for a change in treatment guidelines to minimise discordant therapy. 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