BACKGROUND: The aim of our study was to analyze the factors associated with the increased risk of urinary tract infection (UTI) with carbapenem-resistant (CR) Klebsiella pneumoniae (Kpn) and the antibiotic resistance spectrum of the strains in patients. As secondary objectives, we elaborated the profile of these patients and the incidence of different types of carbapenemases.
METHODS: We conducted a retrospective case-control study in which we compared a group of 62 patients with urinary tract infections with CR Kpn with a control group consisting of 136 patients with urinary tract infections with multidrug-resistant (MDR), but carbapenem-sensitive (CS), Kpn, who were hospitalized between 1 January 2022 and 31 March 2024.
RESULTS: Compared to patients with urinary tract infections with CS Kpn, patients with urinary tract infections with CR Kpn were preponderant in rural areas (62.9% vs. 47.1%, p = 0.038) and more frequently had an upper urinary tract infection (69.4% vs. 36.8%, p < 0.01). Among the risk factors examined, patients in the study group had a higher presence of urinary catheters inserted for up to one month (50% vs. 34.6%, p = 0.03), rate of hospitalization in the last 180 days (96.8% vs. 69.9%, p < 0.01) and incidence of antibiotic therapy in the last 180 days (100% vs. 64.7%, p < 0.01). They also had a higher rate of carbapenem treatment in the last 180 days (8.1% vs. 0%, p < 0.01). Patients in the study group had a broader spectrum of resistance to all antibiotics tested (p < 0.01), with the exception of sulfamethoxazole-trimethoprim, where the resistance rate was similar in both groups (80.6% vs. 67.6%, p = 0.059). In the multivariate analysis, transfer from other hospitals (OR = 3.51, 95% and CI: 1.430-8.629) and treatment with carbapenems in the last 180 days (OR = 11.779 and 95% CI: 1.274-108.952) were factors associated with an increased risk of disease compared to the control group. The presence of carbapenemases was observed in all patients with CR Kpn, in the order of frequency New Delhi metallo-ß-lactamase (NDM) (52.2%), Klebsiella pneumoniae carbapenemase (KPC) (32.6%), and carbapenem-hydrolyzing oxacillinase (Oxa-48) (15.2%).
CONCLUSIONS: The environment of origin and previous treatment with carbapenems appear to be the factors associated with an increased risk of urinary tract infection with CR Kpn compared to patients with urinary tract infections with CS Kpn. CR Kpn exhibits a broad spectrum of antibiotic resistance, among which is resistance to carbapenem antibiotics.

OBJECTIVE: Sulbactam (SBT) is one of the most significant treatments for patients with extensively drug-resistant Acinetobacter baumannii (XDR-AB). However, the efficacy and safety of SBT and its high dose regimen has not been well documented. This retrospective study aimed to assess the efficacy and safety of SBT-based treatment, particularly at high-dose (≥ 6 g/day), for XDR-AB infection.
METHODS: A total of 52 XDR-AB infected patients treated with intravenous SBT at Peking Union Medical College Hospital were included. The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical response and the time of response. The formulation of SBT in our study is 0.5 g per vial.
RESULTS: Among the patients, the 28-day all-cause mortality rate was 36.5% (19/52), and the favorable 14-day clinical response rate was 59.6% (31/52). The 28-day mortality was independently associated coinfection with gram-positive bacteria (GPB) and a shorter duration of therapy. Patients with intracranial infection might have a longer survival time. A favorable 14-day clinical response was associated with the dose of SBT, and a longer treatment duration. However, the higher creatinine clearance (CrCl) associated with a worse clincal response. In addition, a higher SBT dosage was significantly correlated with a shorter time to clinical response. No adverse effects related were reported.
CONCLUSIONS: The single-agent formulation of SBT emerges as a promising alternative for the treatment of XDR-AB infection, such as intracranial infection, particularly at high doses (≥ 6 g/day). Besides, longer duration of treatment correlates with higher survival rate and better favorable clinical response. Higher CrCl negatively correlates with favorable clinical response.

BACKGROUND: Carbapenem-resistant gram-negative bacteria (CRGNB) present a considerable global threat due to their challenging treatment and increased mortality rates, with bloodstream infection (BSI) having the highest mortality rate. Patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT) face an increased risk of BSI. Limited data are available regarding the prognosis and treatment outcomes of CRGNB-BSI in patients with ESRD in intensive care units (ICUs).
METHODS: This multi-center retrospective observational study included a total of 149 ICU patients with ESRD and CRGNB-BSI in Taiwan from January 2015 to December 2019. Clinical and microbiological outcomes were assessed, and multivariable regression analysis was used to evaluate the independent risk factors for day-28 mortality and the impact of antimicrobial therapy regimen on treatment outcomes.
RESULTS: Among the 149 patients, a total of 127 patients (85.2%) acquired BSI in the ICU, with catheter-related infections (47.7%) and pneumonia (32.2%) being the most common etiologies. Acinetobacter baumannii (49.0%) and Klebsiella pneumoniae (31.5%) were the most frequently isolated pathogens. The day-28 mortality rate from BSI onset was 52.3%, and in-hospital mortality was 73.2%, with survivors experiencing prolonged hospital stays. A higher Sequential Organ Failure Assessment (SOFA) score (adjusted hazards ratio [aHR], 1.25; 95% confidence interval [CI] 1.17-1.35) and shock status (aHR, 2.12; 95% CI 1.14-3.94) independently predicted day-28 mortality. Colistin-based therapy reduced day-28 mortality in patients with shock, a SOFA score of ≥ 13, and Acinetobacter baumannii-related BSI.
CONCLUSIONS: CRGNB-BSI led to high mortality in critically ill patients with ESRD. Day-28 mortality was independently predicted by a higher SOFA score and shock status. In patients with higher disease severity and Acinetobacter baumannii-related BSI, colistin-based therapy improved treatment outcomes.

We describe four cases of a novel carbapenem-resistant Pseudomonas aeruginosa ST179 clone carrying the blaKPC-2 or blaKPC-35 gene together with blaIMP-16, imported from Peru to Spain and isolated from leukemia patients. All isolates were multidrug-resistant but remained susceptible to fosfomycin, cefiderocol, and colistin. Whole-genome sequencing revealed that blaKPC-2 and blaKPC-35 were located in an IncP6 plasmid, whereas blaIMP-16 was in a chromosomal type 1 integron. This study highlights the global threat of multidrug-resistant P. aeruginosa clones and underscores the importance of monitoring and early detection of emerging resistance mechanisms to guide appropriate treatment strategies. The importation and spread of such clones emphasize the urgent need to implement strict infection control measures to prevent the dissemination of carbapenem-resistant bacteria.
OBJECTIVE: This is the first documented case of a Pseudomonas aeruginosa ST179 strain carrying the blaKPC-35 gene, and it represents the first report of a P. aeruginosa co-harboring blaIMP-16 and either blaKPC-2 or blaKPC-35, which wre imported from Peru to Spain, highlighting a threat due to the capacity of spreading carbapenem-resistance via plasmid conjugation.

UNASSIGNED: In a previous study, the efficacy and safety of sulbactam-durlobactam vs colistin for the treatment of patients with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRABC) infections were evaluated in a randomized controlled phase 3 trial. Both arms were dosed on a background of imipenem-cilastatin to treat coinfecting gram-negative pathogens. Thirty-six percent of infections in the primary efficacy population were polymicrobial.
UNASSIGNED: A subset analysis was performed to compare clinical and microbiological outcomes at test of cure (7 ± 2 days after the last dose) for patients with monomicrobial and polymicrobial CRABC infections. Minimal inhibitory concentrations of antibiotics against baseline isolates were determined by broth microdilution according to Clinical and Laboratory Standards Institute methodology.
UNASSIGNED: Clinical cure, 28-day all-cause mortality, and microbiological outcomes were similar for patients in the sulbactam-durlobactam treatment arm with monomicrobial or polymicrobial A baumannii-calcoaceticus infections. Patients in the colistin arm with monomicrobial CRABC infections had higher mortality rates with worse clinical and microbiological outcomes as compared with those with polymicrobial infections. For patients who received sulbactam-durlobactam, imipenem susceptibility of coinfecting gram-negative pathogens trended with clinical benefit for patients with polymicrobial A baumannii-calcoaceticus infections. When tested in vitro, durlobactam restored imipenem susceptibility to the majority of coinfecting gram-negative pathogens from the sulbactam-durlobactam arm. This phenotype appeared to be related to the clinical outcome in 13 of 15 evaluable cases.
UNASSIGNED: These results suggest that the use of sulbactam-durlobactam plus a carbapenem could be an effective approach to treat polymicrobial infections that include CRABC, but additional clinical data are needed to demonstrate efficacy.

BACKGROUND: Carbapenem-resistant A. baumannii (CRAB) hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) is now a therapeutic problem worldwide.
METHODS: An open-label, randomized, superiority, single-blind trial was conducted in Rajavithi Hospital, a super-tertiary care facility in Bangkok, Thailand. CRAB HAP/VAP patients were randomly assigned to receive either sitafloxacin-colistin-meropenem or colistin-meropenem. Outcomes in the two groups were then assessed with respect to mortality, clinical response, and adverse effects.
RESULTS: Between April 2021 and April 2022, 77 patients were treated with combinations of either sitafloxacin plus colistin plus meropenem (n = 40) or colistin plus meropenem (n = 37). There were no significant differences between the two groups with respect to all-cause mortality rates at 7 days and 14 days (respectively, 7.5% vs. 2.7%; p = 0.616, and 10% vs. 10%; p = 1). Patients who received sitafloxacin-colistin-meropenem showed improved clinical response compared with patients who received colistin-meropenem in terms of both intention-to-treat (87.5% vs. 62.2%; p = 0.016) and per-protocol analysis (87.2% vs. 67.7%; p = 0.049). There were no significant differences between the two groups with respect to adverse effects.
CONCLUSIONS: Adding sitafloxacin as a third agent to meropenem plus colistin could improve clinical outcomes in CRAB HAP/VAP with little or no impact on adverse effects. In short, sitafloxacin-meropenem-colistin could be another therapeutic option for combatting CRAB HAP/VAP.

OBJECTIVE: To investigate the virulence profiles and identify clinical and microbiological predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii (A. baumannii) bacteremia.
METHODS: This retrospective cohort study enrolled adult patients with carbapenem-resistant A. baumannii (CRAB). Multivariate logistic regression was used to identify the predictors of 30-day mortality. All isolates were subjected to real-time polymerase chain reaction for virulence factors and genotyped using multilocus sequence typing.
RESULTS: Among the 153 patients with CRAB bacteremia, 66 % received appropriate definitive antibiotic therapy. The in-hospital and 30-day mortality rates were 58.3 and 23.5 %, respectively. Ultimately, we enrolled 125 patients with CRAB bacteremia in the analysis, excluding early mortality cases. All CRAB isolates carried blaOXA-23 and blaOXA-51. The clinical strains belonged to 10 sequence types (STs), and the major genotypes were ST191, ST195, ST451, and ST784. The distribution of virulence factors included surface adhesion (Ata, 84.8 %; ChoP, 7.2 %), biofilm formation (OmpA, 76.8 %), killing of host cells (AbeD, 99.2 %), toxins (LipA, 99.2 %), and conjugation (BfmR, 90.4 %). In multivariate logistic regression analysis, hemodialysis due to acute kidney injury and moderate to severe thrombocytopenia were significant risk factors associated with 30-day mortality. However, microbiological factors were not significant predictors.
CONCLUSIONS: Clinical factors such as hemodialysis due to acute renal injury and moderate to severe thrombocytopenia have a greater influence on mortality in CRAB bacteremia compared with microbiological factors.

OBJECTIVE: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly being identified in children, but data on the clinical outcomes in this population are limited. This study aimed to characterise the risk factors for 30-day mortality with CRKP bloodstream infection (BSI) in children.
METHODS: A retrospective study was performed from January 2018 to December 2021 at the First Affiliated Hospital of Zhengzhou University. Patients aged < 18 years and with CRKP BSI were included. Multivariable Cox and logistic regression were performed to determine risk factors for death and the development of septic shock following CRKP infection, respectively.
RESULTS: This study identified 33 neonates aged 0-4 weeks and 37 older children. The 30-day mortality rate was 39.4% in neonates and 43.2% in older children. In the neonatal population, a higher Pitt bacteremia score (HR 1.694; 95% CI 1.313-2.186; P < 0.001) was an independent risk factor for 30-day mortality. In the non-neonatal population, higher platelet count (HR 0.990; 95% CI 0.982-0.998; P = 0.010), the use of carbapenems (HR 0.212; 95% CI 0.064-0.702; P = 0.011) and appropriately targeted antimicrobial treatment (HR 0.327; 95% CI 0.111-0.969; P = 0.044) were associated with decreased 30-day mortality. Monocyte count < 0.1 × 109 cells/L (OR 3.615; 95% CI 1.165-11.444; P = 0.026) and a higher Pitt bacteremia score (OR 1.330; 95% CI 1.048-1.688; P = 0.019) were identified as risk factors for the development of septic shock.
CONCLUSIONS: Carbapenem-resistant Klebsiella pneumoniae BSI was associated with high mortality in children. Appropriate antimicrobial treatment is important to improve survival, but more work is needed to assess the efficacy of specific treatment regimens in children.

Worldwide, hospital-acquired infections (HAIs) are continuously rising within healthcare settings, leading to high mortality and morbidity rates. Many hospitals have reported the spread of carbapenemases globally, specifically within the E. coli and K. pneumoniae species. This study was aimed at analyzing the state of hospital-acquired, carbapenem-resistant E. coli and K. pneumoniae in the United Kingdom between 2009 and 2021. Moreover, the study analyzed the most efficacious approaches to patient management for controlling the carbapenem-resistant Enterobacteriaceae (CRE) spread. Initially, 1094 articles were identified as relevant for screening, and among them, 49 papers were eligible for full-text screening, with a total of 14 articles meeting the inclusion criteria. The information was recorded from published articles through PubMed, the Web of Science, Scopus, Science Direct, and the Cochrane library and was used to search for hospital-acquired carbapenem-resistant E. coli and K pneumoniae in the UK between 2009 and 2021, in order to evaluate the spread of CRE in hospitals. The total number of carbapenem-resistant E. coli was 1083 and this was 2053 for carbapenem-resistant K. pneumoniae in more than 63 UK hospitals. KPC was the dominant carbapenemase produced by K. pneumoniae. The results showed that the treatment options considered depended on the type of carbapenemase produced; K. pneumoniae showed more resistance to a treatment options, i.e., Colistin, than the other carbapenemase. The current state of the UK is at minimal risk for a CRE outbreak; however, appropriate treatment and infection control measures are highly required to prevent this CRE spread at the regional and global levels. The present study findings have an important message for physicians, healthcare workers, and policymakers about hospital-acquired carbapenem-resistant E. coli and K. pneumoniae spread and approaches to patient management.

BACKGROUND: No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections.
METHODS: We conducted an observational retrospective/prospective multicenter study including all patients> 18 years with carbapenem-resistant A. baumannii (CRAB) infections treated with cefiderocol, from June 12021 to October 30 2022. Primary endpoint was 30-day mortality, secondary end-points the clinical and microbiological response at 7 days and at the end of treatment. Furthermore, we compared the clinical and microbiological outcomes among patients who received cefiderocol in monotherapy or in combination.
RESULTS: Thirty-eight patients with forty episodes of infection were included [mean age 65 years (SD+16.3), 75% males, 90% with hospital-acquired infections and 70% showing sepsis or septic shock]. The most common infections included unknown source or catheter-related bacteremia (45%) and pneumonia (40%). We observed at 7 days and at the end of therapy a rate of microbiological failure of 20% and 10%, respectively, and of clinical failure of 47.5% and 32.5%, respectively; the 30-day mortality rate was 47.5%. At multivariate analysis clinical failure at 7 days of treatment was the only independent predictor of 30-day mortality. Comparing monotherapy (used in 72.5%) vs. combination therapy (used in 27.5%), no differences were observed in mortality (51.7 vs 45.5%) and clinical (41.4 vs 63.7%) or microbiological failure (24.1 vs 9.1%).
CONCLUSIONS: The findings of this study reinforce the effectiveness of cefiderocol in CRAB infections, also as monotherapy. However, prospective multicenter studies with larger sample sizes and a control group treated with standard of care are needed to identify the best treatment for CRAB infections.