Carbapenem-resistant Acinetobacter Baumannii Infections Research Articles

Tailoring interventions for control of endemic carbapenem-resistant Acinetobacter baumannii: an interrupted time series analysis

Abstract Background We examined temporal trends in carbapenem-resistant Acinetobacter baumannii (CRAB) infections in one hospital with hyperendemic CRAB, and assessed the efficacy of varied infection control strategies in different ward types. Methods We retrospectively analyzed all CRAB clinical samples from 2006 to 2019, and categorized infections as hospital-onset (HO) or community-onset. We used interrupted time series analysis to assess the impact of interventions on the incidence of all HO-CRAB infections and bloodstream infections (BSI) at the hospital and ward-group levels. Results Over 14 years, 4,009 CRAB infections were identified (89.7% HO), with 813 CRAB BSI (93.2% HO). The incidence per 100,000 patient-days of CRAB infections peaked at 79.1 in 2008, and that of CRAB BSI peaked at 16.2 in 2010. These rates decreased by two-thirds by 2019. In the general ICU, hand hygiene and environmental cleaning interventions were followed by a significant reduction in the level of HO-CRAB infections, with an additional decrease in the slope after the introduction of active surveillance and 2% chlorhexidine bathing. In the surgical ICU and surgical department, a reduction in slope or level of CRAB infection was observed after moving ventilated patients to single rooms. In medical wards, a multi-modal intervention was followed by a reduction in the slope of HO-CRAB infections and BSI. In wards where CRAB infections were uncommon, the incidence of HO-CRAB infections decreased throughout the study period. Conclusion Ward-specific variables determine the success of interventions to reduce CRAB infections; therefore, interventions should be tailored to each setting.

Adaptive resistance to cefiderocol in carbapenem-resistant Acinetobacter baumannii (CRAB): microbiological and clinical issues

ObjectivesDetermining the best available therapy for carbapenem-resistant Acinetobacter baumannii (CRAB) infections is a challenge. Cefiderocol is an attractive alternative drug effective against many resistance mechanisms in Gram-negative bacteria. However, its place in the treatment of Acinetobacter baumannii infections remains unclear and much debated, with contradictory results. MethodsWe describe here the case of a 37-year-old man with ventilator-associated bacteraemic CRAB pneumonia in an intensive care unit. He was initially treated with a combination of colistin and tigecycline, and was then switched onto colistin and cefiderocol. We then used a new accessible protocol to test 30 CRAB isolates (OXA-23/OXA-24/OXA-58/NDM-1) for adaptive resistance to cefiderocol (ARC) after exposure to this drug. ResultsAfter clinical failure with the initial combination, we noted a significant clinical improvement in the patient on the second combination, leading to clinical cure. No ARC was detected in the two OXA-23 case-CRAB isolates. All NDM-1 CRAB isolates were resistant to cefiderocol in standard tests; the OXA-23, OXA-24 and OXA-58 CRAB isolates presented 84.2 %, 50 % and 0 % ARC, respectively. ConclusionsARC is not routinely assessed for CRAB isolates despite frequently being reported in susceptible isolates (69.2 %). Subpopulations displaying ARC may account for treatment failure, but this hypothesis should be treated with caution in the absence of robust clinical data. The two main findings of this work are that (i) cefiderocol monotherapy should probably not be recommended for OXA-23/24 CRAB infections and (ii) the characterisation of carbapenemases in CRAB strains may be informative for clinical decision-making.

Characterization and efficacy against carbapenem-resistant Acinetobacter baumannii of a novel Friunavirus phage from sewage.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a new threat in recent years, owing to its rapidly increasing resistance to antibiotics and new effective therapies are needed to combat this pathogen. Phage therapy is considered to be the most promising alternative for treating CRAB infections. In this study, a novel phage, Ab_WF01, which can lyse clinical CRAB, was isolated and characterized from hospital sewage. The multiplicity of infection, morphology, one-step growth curve, stability, sensitivity, and lytic activity of the phage were also investigated. The genome of phage Ab_WF01 was 41, 317 bp in size with a GC content of 39.12% and encoded 51 open reading frames (ORFs). tRNA, virulence, and antibiotic resistance genes were not detected in the phage genome. Comparative genomic and phylogenetic analyses suggest that phage Ab_WF01 is a novel species of the genus Friunavirus, subfamily Beijerinckvirinae, and family Autographiviridae. The in vivo results showed that phage Ab_WF01 significantly increased the survival rate of CRAB-infected Galleria mellonella (from 0% to 70% at 48 h) and mice (from 0% to 60% for 7 days). Moreover, after day 3 post-infection, phage Ab_WF01 reduced inflammatory response, with strongly ameliorated histological damage and bacterial clearance in infected tissue organs (lungs, liver, and spleen) in mouse CRAB infection model. Taken together, these results show that phage Ab_WF01 holds great promise as a potential alternative agent with excellent stability for against CRAB infections.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.

Characteristics of drug resistance and biofilm formation in carbapenem-resistant Acinetobacter baumannii in hospitalized children

To study the distribution, drug resistance, and biofilm characteristics of carbapenem-resistant Acinetobacter baumannii (CRAB) isolated from hospitalized children, providing a reference for the prevention and treatment of CRAB infections in hospitalized children. Forty-eight CRAB strains isolated from January 2019 to December 2022 were classified into epidemic and sporadic strains using repetitive extragenic palindromic sequence-based polymerase chain reaction. The drug resistance, biofilm phenotypes, and gene carriage of these two types of strains were compared. Both the 22 epidemic strains and the 26 sporadic strains were producers of Class D carbapenemases or extended-spectrum β-lactamases with downregulated outer membrane porins, harboring the VIM, OXA-23, and OXA-51 genes. The biofilm formation capability of the sporadic strains was stronger than that of the epidemic strains (P<0.05). Genes related to biofilm formation, including Bap, bfs, OmpA, CsuE, and intI1, were detected in both epidemic and sporadic strains, with a higher detection rate of the intI1 gene in epidemic strains (P<0.05). CRAB strains are colonized in the hospital, with sporadic strains having a stronger ability to form biofilms, suggesting the potential for forming new clonal transmissions in the hospital. Continuous monitoring of the epidemic trends of CRAB and early warning of the distribution of epidemic strains are necessary to reduce the risk of CRAB infections in hospitalized children.

The antibacterial effect mechanisms of Laurus nobilis extracts on carbapenem-resistant Acinetobacter baumanii isolates

Carbapenem-resistant Acinetobacter baumannii infections are becoming increasingly difficult to treat. Thus, this paper focused on identification of carbapenemase genes in carbapenem-resistant A. baumanii isolates, determining the antibacterial activities of Laurus nobilis L. leaves extracts in both carbapenem-sensitive and resistant strains, and comparing MIC values in strains with various carbapenemase genotypes. Besides, the components of Laurus nobilis extracts and the theoretical calculation of the antibacterial effect mechanisms of Laurus nobilis extracts on A. baumanii isolates were investigated. The MIC value of Laurus nobilis extracts was found to be 250 μg/ml in A. baumanii isolates carrying one or two carbepenemase genes, while the MIC value was found to be 500 μg/ml in strains carrying three or more carbapenemase genes. The extracts of Laurus nobilis had the highest concentration of rutin, followed by ferulic acid. The interaction of the major component of the extract, rutin, with OXA-51 was explored by molecular docking to demonstrate its binding potential. Its interaction was then compared to the interaction of a standard drug (doripenem). The binding potential of rutin was found to be slightly higher than that of doripenem that reflected the limited activity of the extract on the carbapenem-resistant strains. Consequently, new treatment drugs have needed to limit the spread of carbapenem-resistant A. baumannii.

Phytochemical Composition and Antimicrobial Efficacy of Salvadora persica Root Extracts Against Carbapenem-Resistant Acinetobacter baumannii.

Background Carbapenem-resistant Acinetobacter baumannii (CRAB) are difficult to eradicate from the environment and are virtually immune to all antibiotics. Consequently, CRABmay culminate in severe outbreaks and fatal infections among people attending hospitals and nursing homes. Salvadora persicahas been used as an herbal remedy and chewing sticks for dental cleansing.Evaluating S.persica's efficacy against CRABmay provide an alternative approach to treating CRAB infections in healthcare environments, considering its traditional application in dental hygiene. Employing S. persica as an herbal remedy could be a part of a more sustainableapproach to control CRAB infections. Aim To investigate the phytochemical composition of S. persica and evaluate its antimicrobial properties. Materials and methods The roots were extracted by Soxhlet apparatus using n-hexane, chloroform, and methanol. Each extract was analyzed using gas chromatography-mass spectrometry (GCMS) and characterized using WN908.Land National Institute of Standards and Technology (NIST) libraries.The antimicrobial activity of each extract against CRAB was evaluated using a broth microdilution assay to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results The GCMS analysis of different solvent extracts of S. persica roots showed the presence of various phytochemical compounds such as steroids, phenolic compounds, fatty acids, alcohols, terpenoids, and vitamin E. Both chloroform and hexane extracts showed the most effective antimicrobial activity with a MIC valueof 3.13 mg/mL and an MBC value of 12.50 mg/mL, respectively. Benzoic acid was the major phytochemical compound identified from S. persica extract. N-hexane, chloroform, and methanol extracts exhibited maximum antimicrobial activity due to the presence of active compounds in them. Conclusion Chloroform and hexane extracts showed the most potent antibacterial activities against CRAB.

Intravenous fosfomycin for treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: a multicenter clinical experience

Backgroundsevere infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have been increasingly reported over the past few years. Many in vivo and in vitro studies suggest a possible role of intravenous fosfomycin for the treatment of CRAB infections. Methodsthis multicenter, retrospective study included patients treated with intravenous fosfomycin for severe infections caused by CRAB admitted consecutively from December 2017 to December 2022 in four Hospitals in Italy. The primary goal of the study was to evaluate the risk factors associated with 30-day mortality in the study population. A propensity score matched analysis was added to the model. Resultsduring the study period, 102 patients with severe infection caused by CRAB treated with an intravenous fosfomycin-containing regimen were enrolled: ventilator-associated pneumonia (VAP) was diagnosed in 59% of patients, primary bacteremia in 22%, and CVC-related infection in 16%. All patients were treated with a regimen containing intravenous fosfomycin, mainly in combination with cefiderocol (n=54), colistin (n=48), and ampicillin/sulbactam (n=18). Forty-eight (47%) patients died within 30 days. Fifty-eight (57%) patients experienced a clinical therapeutic failure. Cox regression analysis showed that diabetes, primary bacteraemia, and a colistin-containing regimen were independently associated with 30-day mortality, whereas an adequate source control of infection, an early 24 h active in vitro therapy, and a cefiderocol-containing regimen were associated with survival. A colistin-based regimen, A. baumannii colonization and primary bacteremia were independently associated with clinical failure. Conversely, an adequate source control of infection, a cefiderocol-containing regimen, and an early 24 h active in vitro therapy were associated with clinical success. ConclusionsOur data showed different antibiotic regimens containing fosfomycin in combination treatment of severe infections caused by CRAB.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

High-Loading-Dose Colistin with Nebulized Administration for Carbapenem-Resistant Acinetobacter baumannii Pneumonia in Critically Ill Patients: A Retrospective Cohort Study.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections pose a serious threat, with high morbidity and mortality rates. This retrospective cohort study, conducted at Nakornping Hospital between January 2015 and October 2022, aimed to evaluate the efficacy and safety of a high loading dose (LD) of colistin combined with nebulized colistin in critically ill patients with CRAB pneumonia. Of the 261 patients included, 95 received LD colistin, and 166 received LD colistin with nebulized colistin. Multivariate Cox regression analysis, adjusted for baseline covariates using inverse probability weighting, showed no significant difference in 30-day survival between patients who received LD colistin and those who received LD colistin with nebulized colistin (adjusted hazard ratio [aHR]: 1.17, 95% confidence interval [CI]: 0.80-1.72, p = 0.418). Likewise, there were no significant differences in clinical response (aHR: 0.93, 95% CI: 0.66-1.31, p = 0.688), microbiological response (aHR: 1.21, 95% CI: 0.85-1.73, p = 0.279), or nephrotoxicity (aHR: 1.14, 95% CI: 0.79-1.64, p = 0.492) between the two treatment groups. No significant adverse events related to nebulized colistin were reported. These findings suggest that the addition of nebulized colistin may not offer additional benefits in terms of 30-day survival, clinical or microbiological response, or nephrotoxicity in these patients.

Risk factors and genetic characteristics of the carriage of hypervirulent and carbapenem-resistant Acinetobacter baumannii among pregnant women.

Carbapenem-resistant Acinetobacter baumannii (CRAB) and its emerging evolutionary branch toward hypervirulence have been neglected in pregnancy. From September 2020 to August 2021, an active surveillance culture program encompassed 138 randomly selected pregnant women, with five subjected to sample collection at two different time points. The clinical characterization was explored through statistical analysis. Whole-genome sequencing, a Galleria mellonella infection model, and a global database were used to investigate the genetic characterization, pathogenicity, evolutionary history, and phylogenetic relationships of the isolates. Of the 41 CRAB isolates obtained, they were divided into four ClustersRS and an orphan pattern. ClusterRS 1 (n = 31), with eight complex types in pregnancy, was also the dominant ClusterRS globally, followed by ClusterRS 13 (n = 5), identified as hypervirulent KL49 CRAB, exhibiting phylogeographical specificity to Guangdong. A maternal carriage CRAB rate of 26.09% (36/138) was revealed, with half of the isolates representing novel complex types, prominently including CT3071, as the first KL7 isolates identified in Shenzhen. Both KL49 and KL7 isolates were most commonly found in the same participant, suggesting potential intraspecific competition as a possible reason for CRAB infection without carriers during pregnancy. The independent risk factors for carriers were revealed for the first time, including advanced maternal age, gestational diabetes mellitus, and Group B Streptococcus infection. The significant carriage rate and enhanced virulence of CRAB during pregnancy emphasize the imperative for routine surveillance to forestall dissemination within this high-risk group, especially in Guangdong for ClusterRS 13 isolates.

Antimicrobial peptide DvAMP combats carbapenem-resistant Acinetobacter baumannii infection

Carbapenem-resistant Acinetobacter baumannii (CRAB), an important opportunistic pathogen, is a major cause of healthcare-associated infections. The polymyxins (colistin and polymyxin B) are the last line of defense in the treatment of CRAB infections, and there is an urgent need to develop novel alternative therapeutic strategies. In this study, we found that the antimicrobial peptide DvAMP exhibited satisfactory antibacterial and antibiofilm activity against CRAB. In addition, DvAMP showed tolerable stability in salt ions and serum and exhibited low toxicity in vivo. Investigation of the underlying mechanism demonstrated that DvAMP disrupts cell membrane structural integrity and specifically binds to exogenous lipopolysaccharides (LPS) and phospholipids (PG/CL), resulting in increased membrane permeability and dissipating proton motive force (PMF), further reducing intracellular ATP levels and inducing ROS accumulation, leading to bacterial death. Furthermore, DvAMP therapy efficiently improved survival rates and decreased the bacterial load in the lungs of mice in a mouse pneumonia model, showing that DvAMP administration reduced CRAB susceptibility to lung infection. These results indicate that the peptide DvAMP is a promising alternative therapeutic agent to combat CRAB infection.

A retrospective analysis of carbapenem-resistant Acinetobacter baumannii infections in critically ill patients: Experience at a tertiary-care teaching hospital ICU

BackgroundAcinetobacter baumannii is a clinically significant pathogen with a high incidence of multidrug resistance that is associated with life-threatening nosocomial infections. Here, we aimed to provide an insight into the clinical characteristics and outcomes of a unique group of A. baumannii infections in which the isolates were resistant to carbapenems and most other antibiotic groups in a tertiary-care intensive care unit (ICU). MethodsWe performed a retrospective observational study in which records of patients hospitalized in the ICU between June 1, 2021 and June 1, 2023 were reviewed. We checked the clinical, laboratory, and microbiological records of all adult patients who had carbapenem-resistant A. baumannii (CRAB) infections. Prior antibiotic treatments and definitive antibiotic treatments after culture positivity and susceptibility test results were recorded. C-reactive protein (CRP) and procalcitonin levels and leukocyte counts were noted. Length of ICU stay and 30-day mortality were defined as the outcome parameters. ResultsDuring the study period, 57 patients were diagnosed with CRAB infections. The respiratory tract was the leading infection site (80.7%). In non-survivors, bloodstream infections (21.9% vs. 4.0% P=0.05) and colistin-resistant (col-R) CRAB infections (43.8% vs. 24.0%, P=0.12) were more common than in survivors, but these parameters were not statistically significant. The length of ICU stay was not different between survivors and non-survivors. Overall, the rate of col-R among CRAB clinical isolates was 35.1%. The 30-day mortality in all patients with CRAB infection was 56.1%. Mortality in col-R CRAB and colistin-susceptible (col-S) CRAB infections was 70.0% and 48.6%, respectively (P=0.12). Prior carbapenem use was 56.1%. Prior colistin use before col-R and col-S CRAB infections was not significant (35.0% vs. 27.0%, P=0.53). ConclusionsOur study provides real-world data on highly resistant A. baumannii infections and shares the characteristics of infections with such resistant strains. Unfortunately, carbapenem resistance in A. baumannii is a challenge for intensive care specialists who are faced with few treatment options, and colistin resistance further complicates the problem.

Carbapenem-resistant Acinetobacter baumannii Outbreak in a COVID-19 Isolation Ward and Successful Outbreak Control with Infection Control Measures.

Even amid the coronavirus disease-19 (COVID-19) pandemic, the spread of multidrug-resistant bacteria and infection control are still important tasks. After recognizing the carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak that occurred in the isolation room for COVID-19, we would like to introduce what infection control measures were implemented to eradicate it. All COVID-19 patients with CRAB in any specimen admitted to the COVID-19 isolation ward of the tertiary hospital in South Korea from October to November 2021 were analyzed. During the outbreak, 23 patients with COVID-19 and CRAB infections were identified. The index case was an 85-year-old female referred from a long-term care facility. CRAB was identified in sputum culture in most patients (91.3%). The CRAB outbreak occurred mainly in the rooms around the index case. Environmental cultures on the floor, air inlet, air outlet, and window frame of the rooms were performed. The antimicrobial resistance patterns of CRAB from patients and the environment were identical; whole-genome sequencing analyses revealed isolated clonality. Infection control measures with enhanced environmental cleaning using 1,000 ppm sodium hypochlorite and phenolic compounds, enhanced hand hygiene, additional education, and mandatory additional gowning and gloving of COVID-19 personal protective equipment (PPE) were applied on 29 October. No CRAB infection cases occurred from 2 November for two weeks. In addition to applying PPE and COVID-19 precautions in COVID-19 isolation wards, adhering to strict contact precautions along with environmental control can help prevent the spread of multidrug-resistant bacteria.

Cefiderocol and Sulbactam-Durlobactam against Carbapenem-Resistant Acinetobacter baumannii.

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) remain a clinical challenge due to limited treatment options. Recently, cefiderocol, a novel siderophore cephalosporin, and sulbactam-durlobactam, a bactericidal β-lactam-β-lactamase inhibitor combination, have been approved by the Food and Drug Administration for the treatment of A. baumannii infections. In this review, we discuss the mechanisms of action of and resistance to cefiderocol and sulbactam-durlobactam, the antimicrobial susceptibility of A. baumannii isolates to these drugs, as well as the clinical effectiveness of cefiderocol and sulbactam/durlobactam-based regimens against CRAB. Overall, cefiderocol and sulbactam-durlobactam show an excellent antimicrobial activity against CRAB. The review of clinical studies evaluating the efficacy of cefiderocol therapy against CRAB indicates it is non-inferior to colistin/other treatments for CRAB infections, with a better safety profile. Combination treatment is not associated with improved outcomes compared to monotherapy. Higher mortality rates are often associated with prior patient comorbidities and the severity of the underlying infection. Regarding sulbactam-durlobactam, current data from the pivotal clinical trial and case reports suggest this antibiotic combination could be a valuable option in critically ill patients affected by CRAB infections, in particular where no other antibiotic appears to be effective.

Clinical efficacy of cefiderocol-based regimens in patients with carbapenem-resistant Acinetobacter baumannii infections: A systematic review with meta-analysis

ObjectivesTo perform a systematic review with meta-analysis to assess the clinical efficacy of cefiderocol-based regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. MethodsTwo authors independently searched PubMed-MEDLINE, Scopus, and Cochrane databases, from inception to 02 July 2023, for randomised controlled trials (RCTs) or observational studies comparing clinical efficacy of cefiderocol-based vs. non-cefiderocol-based regimens in patients with CRAB infections. Data were extracted by the two authors independently, and the quality of included studies was independently assessed using ROB 2.0 or ROBINS-I tools. Primary outcome was mortality rate. Meta-analysis was performed by pooling odds ratios (ORs) retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity. ResultsA total of 530 articles were screened, and 6 studies (1 RCT and 5 observational; N=561; 247 cefiderocol-based vs. 314 non-cefiderocol-based regimens) were included. Cefiderocol did not significantly reduce in-hospital mortality compared to alternative therapies (predominantly colistin-based), but the confidence intervals around the effect estimate included clinically important benefit (N=5; OR 0.64; 95%CI 0.40–1.04; I2=57.5%). When only observational studies providing adjustment for confounders were considered, a lower risk of mortality was found in patients treated with cefiderocol-based regimens (N=4; OR 0.53; 95%CI 0.39–0.71; I2=0.0%). ConclusionsCefiderocol-based regimens were associated with a significantly lower risk of mortality in patients with CRAB infections in observational studies providing proper adjustment for confounders.

Insights into the epidemiology, risk factors, and clinical outcomes of carbapenem-resistant Acinetobacter baumannii infections in critically ill children.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a leading cause of nosocomial infections with an increasing impact on critically ill patients, yet there is limited data on contributing factors. This study was aim to evaluate the prevalence and risk factors, and clinical outcomes of CRAB infections among critically ill children in a tertiary university teaching hospital in China. From January 2016 to December 2021, all children diagnosed with nosocomial Acinetobacter baumannii (A. baumannii) infections in the pediatric intensive care unit (PICU) were identified through the computerized microbiology laboratory databases. Among them, children suffering from CRAB infection were designated as a case group, while children with carbapenem susceptible A. baumannii (CSAB) infection were assigned to a control group. This retrospective case-control study was based on two groups of patients to determine potential clinical factors contributing to CRAB infection and death among critically ill children via univariate and multivariate analyses. During the 6-year study period, a total of 372 episodes of nosocomial A. baumannii infection in the PICU were eligible and included in the study. These isolates displayed moderate or high rates of resistance to all tested antimicrobials except colistin. The overall prevalence of CRAB and MDRAB (multidrug-resistant A. baumannii) was 78.0% and 80.9%, respectively. Several risk factors found to significantly increase CRAB infection included receiving invasive operation (OR = 9.412, p = 0.001), gastric intubation (OR = 2.478, p = 0.026), prior carbapenems exposure (OR = 2.543, p = 0.003), severe pneumonia (OR = 3.235, p = 0.001), and hemoglobin <110g/L (OR = 3.049, p = 0.005). Of 372 patients with CRAB infection, the mortality rate was 30.9% (115/372) and mortality did not differ between children with CRAB and CSAB infections. Septic shock (OR = 2.992, p = 0.001), AST > 46U/L (OR = 2.015, p = 0.005), bone marrow aspiration (OR = 2.704, p = 0.008), lymphocyte <20 % (OR = 1.992, p = 0.006) and age (OR = 1.094, p = 0.002) were independent risk factors for the death of A. baumanni infection. This study highlights considerable incidence rate and remarkable mortality of children with A. baumanni (especially CRAB) infections, and identifies age-specific risk factors for CRAB infection and mortality in critically ill children. These risk factors should be taken into account in pediatric hospitals in order to establish early intervention and rational treatment to improve clinical outcomes.

Efficacy of combination therapy with standard-dose carbapenem for treating nosocomial pneumonia caused by carbapenem-resistant Acinetobacter baumannii in intensive care units: A multicentre retrospective propensity score-matched study

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is common worldwide. Despite carbapenem resistance, standard-dose carbapenems are still used in clinical practice. Hence in this study, we aimed to compare the efficacy and outcomes of a regimen containing standard-dose carbapenems with those of a regimen lacking carbapenems during the treatment of critically ill patients with CRAB nosocomial pneumonia in the intensive care unit (ICU). Initially, 735 patients were recruited for this multicentre retrospective cohort study. After exclusion, time-window bias adjustment, and propensity score matching, multiple clinical outcomes were compared between the carbapenem-containing (CC) (n = 166) and no carbapenem-containing (NCC) (n = 166) groups. The CC group showed a higher risk of clinical failure on day 7 than the NCC group (44.6% vs. 33.1%, P = 0.043). The lengths of ICU stay (21 and 16 days, P = 0.024) and hospital stay (61 and 44 days, P = 0.003) were longer in the CC group than in the NCC group. Multivariate analysis showed that the CC regimen was associated with higher clinical failure (adjusted odds ratio (aOR) = 1.64, 95% CI = 1.05–2.56, P = 0.031) and lower microbiological eradication (aOR = 0.48, 95% CI = 0.23–1.00, P = 0.049) at day 7 than the NCC group. Thus, a regimen containing a standard dose of carbapenem should be prescribed with caution for treating CRAB nosocomial pneumonia in the ICU.

2759. Cefiderocol vs Best Available Therapy for the Treatment of Carbapenem- Resistant Acinetobacter baumannii

Abstract Background Cefiderocol has been evaluated as a treatment of carbapenem-resistant gram negative infections. However robust data for the optimal approach to treat carbapenem-resistant Acinetobacter baumannii (CRAB) is lacking. The purpose of this study was to evaluate the efficacy of cefiderocol vs best available therapy (BAT) for the treatment CRAB infections. Methods This IRB-approved retrospective observational review was conducted at a three-hospital community health system between June, 2020 to February, 2021. Hospitalized patients were included if they were ≥18 years old and received ≥24 hours of targeted antibiotics for CRAB. Patients were excluded if they were considered to be colonized or were pregnant. Patients in the cefiderocol group were matched with patients in BAT group based on age and source of infection in a 1:3 ratio. The primary endpoint of this study was to assess all-cause inpatient mortality (ACIM) at the end of therapy. The secondary endpoint included clinical cure (CC) at the end of therapy. A subgroup analysis was performed for patients treated with cefiderocol monotherapy, cefiderocol combination therapy, and combination BAT to determine differences in ACIM and CC. Results A total of 60 patients were included in the primary analysis; 15 receiving cefiderocol and 45 receiving BAT. There was no difference in patient age, race, and diagnosis between both groups. Patients in the BAT group had a shorter length of stay vs cefiderocol group (14 vs 19 days. P=0.05). Ampicillin/sulbactam (86.7% vs 57.8%, P=0.06) and minocycline (86.7% vs 22.2%, P=0.0001) non-susceptible CRAB isolates were more common in the cefiderocol group vs BAT group (as seen in Figure 1). No differences were seen in ACIM (27% vs 18%, P=0.47) and CC (53% vs 60%, P=1.0) between both groups. The subgroup analysis revealed cefiderocol combination therapy had a decreased number of patients with ACIM and had favorable CC outcomes compared to cefiderocol monotherapy and combination BAT (as seen in Figure 2). Comparison of Susceptibility Patterns All Cause Inpatient Mortality and Clinical Cure in Subgroup Analysis of Monotherapy vs Combination Therapy Conclusion Cefiderocol seems to be a viable option for treatment of CRAB infections. No differences were seen in ACIM and CC between cefiderocol and BAT. Cefiderocol combination therapy seems to be a preferred therapeutic option for CRAB infections. Disclosures All Authors: No reported disclosures

A Retrospective Case-Control Study of Eravacycline for the Treatment of Carbapenem-Resistant Acinetobacter Infections in Patients With Burn Injuries.

Thermal injuries lead to a deficiency in one's natural, protective barrier, resulting in increased susceptibility to pathogens, and often require multiple courses of broad-spectrum antibiotics. Eravacycline (ERA) has shown adequate in vitro activity against multiple multi-drug resistant (MDR) pathogens including Acinetobacter sp. Due to the increasing prevalence of MDR bacteria and the heightened susceptibility of patients with burns to infection, studies are needed to examine the clinical effect of eravacycline in this population. The objective of this retrospective, case-control study was to compare the outcomes of patients with thermal injuries treated with eravacycline versus a matched control for carbapenem-resistant Acinetobacter baumannii (CRAB) infections. Patients with thermal injury admitted to an American Burn Associated-verified burn center from May 1, 2019 to July 31, 2022, who received eravacycline, were randomly matched 4:1 to a historical cohort using a previously established, de-identified dataset of patients treated with colistimethate sodium (CMS) in the same burn center (March 1, 2009 to March 31, 2014), based on % total body surface area (%TBSA), age, and CRAB. A composite favorable outcome was defined as 30-day survival, completion of the course, lack of 14-day recurrence, and lack of acute kidney injury (AKI). Treatment with eravacycline over CMS was not more or less likely to be associated with a favorable response [odds ratio (95% confidence interval), 2.066 (0.456-9.361), P = .347]. Patients treated with CMS had nearly 9-fold higher odds of new-onset AKI versus ERA [8.816 (0.911-85.308), P = .06]. Adverse events were uncommon in the ERA group. There was no difference in mortality.