Gtr9 mutation trades phage resistance for carbapenem sensitivity to potentiate phage-meropenem therapy against carbapenem-resistant Acinetobacter baumannii in vitro.

A multicenter study of risk factors and outcome of hospitalized patients with infections due to carbapenem-resistant Acinetobacter baumannii

Risk Factors of Carbapenem-resistant Acinetobacter baumannii Infection among Hospitalized Patients

Active surveillance for carbapenem-resistant Acinetobacter baumannii in a medical intensive care unit: Can it predict and reduce subsequent infections and the use of colistin?

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.

Objective To assess the risk factors of carbapenem-resistant Acinetobacter baumannii (CRAB) infection. Methods Clinical data of patients with positive bacterial culture in Tianjin Medical University General Hospital during January 2011 and December 2015 were retrospectively analyzed, including 68 patients with carbapenem resistant Acinetobacter baumannii (CRAB) bacteremia, 68 patients with carbapenem sensitive Acinetobacter baumannii (CSAB) bacteremia, and 68 patients with positive culture of other bacteria (control group). The risk factors of Acinetobacter baumannii infection were analyzed by univatiate and multivariate Logistic regression analyses. Results Univariate analysis showed that bacteremia/sepsis, use of carbapenems, β-lactamase inhibitor compound, tigecycline, combined antibiotics, glucocorticoids, surgery within one month, mechanical ventilation, central venous catheters(CVCs), arteriopuncture, indwelling catheter≥3 days and indwelling gastric tube were risk factors of CRAB infection (CRAB vs. control: χ2=4.96, 15.56, 7.64, 9.22, 5.89, 6.80, 17.00, 11.83, 18.22, 8.24, 25.24 and 7.70, P<0.05 or P<0.01, respectively); while use of third-generation cephalosporin, CVCs, length of hospital stay were risk factors of CSAB infection (CSAB vs. control: χ2=11.93 and 6.94, U=1555, P<0.05). Multivariate logistic analysis showed that bacteremia/sepsis (OR=4.01, 95%CI: 1.13~14.20), use of carbapenems (OR=4.17, 95%CI : 1.79~9.73), CVCs (OR=2.93, 95% CI: 1.22~7.08), indwelling catheter≥3 days (OR=6.08, 95%CI: 2.39~15.46) were independent risk factors of CRAB infection; use of third-generation cephalosporin (OR=3.98, 95% CI : 1.88~8.43 ), CVCs(OR=3.40, 95% CI: 1.48~7.81) were independent risk factors of CSAB infection. Conclusions Long-term use of carbapenems and invasive procedures are associated with CRAB infection, strict control of invasive procedures and rational use of antibiotics may reduce CRAB infection. Key words: Acinetobacter baumannii; Drug resistance, multiple; Risk factors; Case-case-control study

We examined temporal trends in carbapenem-resistant Acinetobacter baumannii (CRAB) infections in a hospital with hyperendemic CRAB and assessed the efficacy of varied infection control strategies in different ward types. 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 (BSIs) at the hospital and ward group levels. Over 14 years, 4009 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 in 2008 at 79.1, and that of CRAB BSI peaked in 2010 at 16.2. These rates decreased by two-thirds by 2019. In the general intensive care unit (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 multimodal intervention was followed by a reduction in the slope of HO-CRAB infections and BSIs. In wards where CRAB infections were uncommon, the incidence of HO-CRAB infections decreased throughout the study period. Ward-specific variables determine the success of interventions in reducing CRAB infections; therefore, interventions should be tailored to each setting.

Phage-conjugated chlorin e6: A strategy overcoming phage resistance in biofilm eradication and wound infection therapy of carbapenem-resistant Acinetobacter baumannii.

BackgroundDuring the Coronavirus Disease 2019 (COVID-19) epidemic, the strain on intensive care units (ICUs) has increased, which made them more vulnerable to the threat of multidrug-resistant organism (MDRO).AimThis study aims to investigate an outbreak of carbapenem resistant Acinetobacter baumannii (CRAB) infection in a general adult ICU of a tertiary hospital in China during the COVID-19 epidemic and evaluate the effectiveness of intervention measures.MethodsDemographic and clinical data of 37 patients were collected, and 230 environmental samples were collected. Whole genome sequencing (WGS) analysis was performed on clinical and environmental isolates. An evolutionary tree was constructed based on the WGS data. The infection control team implemented a bundle of MDRO interventions, including a termination of COVID-19 infection control measures and implementation of ‘three-step’ cleaning and disinfection method.FindingsThere were 37 patients found to have CRAB infection or colonization in the ICU from December 2022 to April 2023, of whom 35 were hospital-acquired. 12 CRAB isolates were obtained from the environment and medical equipment. Through WGS analysis, the CRAB strains from the medical environment and bronchoscopes were found to be highly homologous to those from patients’ clinical specimens. This demonstrated that the infection outbreak was caused by the lack of MDRO prevention and control measures. Following intervention, the CRAB detection rate gradually declined, with no positive samples for CRAB found in the ICU environment or on bronchoscopes.ConclusionThe infection control measures for COVID-19 conflicted with basic MDRO prevention and control strategies, likely contributing to the outbreak. Therefore, established infection prevention and control measures should be consistently followed, as they represent the most effective approach to preventing MDRO.

In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become one of the leading causes of healthcare-associated infections globally, particularly in intensive care units (ICUs). Cross-transmission of microorganisms between patients and the hospital environment may play a crucial role in ICU-acquired CRAB colonization and infection. The control and treatment of CRAB infection in ICUs have been recognized as a global challenge because of its multiple-drug resistance. The main concern is that CRAB infections can be disastrous for ICU patients if currently existing limited therapeutic alternatives fail in the future. Therefore, the colonization, infection, transmission, and resistance mechanisms of CRAB in ICUs need to be systematically studied. To provide a basis for prevention and control countermeasures for CRAB infection in ICUs, we present an overview of research on CRAB in ICUs, summarize clinical infections and environmental reservoirs, discuss the drug resistance mechanism and homology of CRAB in ICUs, and evaluate contemporary treatment and control strategies.

Infection with carbapenem-resistant Acinetobacter baumannii (CRAB) after liver transplantation (LT) is associated with high mortality. This study aimed to identify risk factors for post-LT CRAB infection, as well as to evaluate the impact of pre-LT CRAB acquisition on the incidence of post-LT CRAB infection. This was a prospective cohort study of all patients undergoing LT at our facility between October 2009 and October 2011. Surveillance cultures (SCs) were collected immediately before LT and weekly thereafter, until discharge. We analyzed 196 patients who were submitted to 222 LTs. CRAB was identified in 105 (53.6%); 24 (22.9%) of these patients were found to have acquired CRAB before LT, and 85 (81.0%) tested positive on SCs. Post-LT CRAB infection occurred in 56 (28.6%), the most common site being the surgical wound. Multivariate analysis showed that the risk factors for developing CRAB infection were prolonged cold ischemia, post-LT dialysis, LT due to fulminant hepatitis, and pre-LT CRAB acquisition with pre-LT CRAB acquisition showing a considerable trend toward significance (P = 0.06). Among the recipients with CRAB infection, 60-day mortality was 46.4%, significantly higher than among those without (P < 0.001). Mortality risk factors were post-LT infection with multidrug-resistant bacteria, LT performed because of fulminant hepatitis, retransplantation, prolonged cold ischemia, longer LT surgical time, and pre-LT CRAB acquisition, the last showing a trend toward significance (P = 0.08). In conclusion, pre-LT CRAB acquisition appears to increase the risk of post-LT CRAB infection, which has a negative impact on recipient survival. Liver Transplantation 22 615-626 2016 AASLD.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is becoming more widely recognized as a serious cause of nosocomial infections, and colistin has been reintroduced in recent years for the treatment of CRAB infection. Combinations of colistin and meropenem or imipenem have been found to be effective against CRAB isolates, whereas clinical investigations have not definitively demonstrated the theoretical benefits of colistin combined therapy in patients with CRAB infections. The objective of this study was to compare the primary outcome (30-day survival rate) and secondary outcomes (clinical response, microbiological response and nephrotoxicity) between patients who received loading dose (LD) colistin–meropenem and LD colistin–imipenem for the treatment of CRAB infection. A retrospective cohort analysis was performed at Chiang Mai University Hospital in patients with CRAB infection who received LD colistin–meropenem or LD colistin–imipenem between 2011 and 2017, and 379 patients fulfilled the requirements for the inclusion criteria. The results of this study showed that patients who received LD colistin–imipenem had a lower 30-day survival rate (adjusted HR = 0.57, 95% CI: 0.37–0.90; p = 0.015) and a lower clinical response (aHR = 0.56, 95% CI: 0.35–0.90; p = 0.017) compared with those who received LD colistin–meropenem. The microbiological response in patients with LD colistin–imipenem was 0.52 times (aHR) lower than that in those who received colistin–meropenem (95% CI: 0.34–0.81; p = 0.004); however, there was no significant difference in nephrotoxicity (aHR = 1.03, 95% CI: 0.67–1.57; p = 0.897) between the two combination regimens. In conclusion, when comparing the combination of LD colistin with imipenem or meropenem, the combination of LD colistin and meropenem provides a better survival rate for treating CRAB. Thus, we suggest that combinations of LD colistin and meropenem should be considered when treating CRAB infections.

BackgroundThe global threat of Carbapenem-resistant Acinetobacter baumannii (CRAB) has intensified as resistance to carbapenems continues to rise in recent decades. We aimed to explore risk factors, molecular epidemiology, and antimicrobial therapy of CRAB infection.MethodsThe clinical data of 110 patients infected with A. baumannii from December 2021 to December 2022 were retrospectively analyzed. Patients were divided into a carbapenem-resistance group (55 patients) and carbapenem-sensitive group (CSAB; 55 patients) based on resistance to carbapenem, and the risk factors of patients infected with CRAB were analyzed. Fifty-five patients with CRAB infection who received antimicrobial therapy were divided into a combination therapy group (45 patients) and a monotherapy group (10 patients), and differences between the two groups were compared. Whole-genome sequencing analysis was performed to assess resistance genes. Phylogenetic analysis was performed to explore the characteristics of CRAB isolates.ResultsAmong the total 110 patients, the rate of poor prognosis in the CRAB group was 43.6% (24/55). Mechanical ventilation (odds ratio [OR] = 5.364, 95% confidence interval [CI] 1.462–19.679, P = 0.011) and puncture (OR = 19.935, 95% CI 1.261–315.031, P = 0.012) were independent risk factors for CRAB infection. Of 55 patients in the antimicrobial regimen study, 45 received combination therapy (including dual, triple, or quadruple antibiotic therapy) and 10 received monotherapy. Univariate analysis revealed significant differences between the combination group and monotherapy group for admission to the intensive care unit and wound infection (P < 0.05). The CRAB strains of 26 patients taking carbapenem-based combination therapy were mainly ST208, ST1968, and ST195, among which patients with ST1968 strains had higher 28-day mortality. Furthermore, the blaOXA−23 gene was harbored in ST1968, ST195, and ST208.ConclusionsMortality was significantly higher in patients infected with CRAB than with CSAB. Mechanical ventilation and puncture were independent risk factors in predicting CRAB infections. The distribution of CRAB was dominated by ST208, ST1968, and ST195, among which patients with ST1968 had higher 28-day mortality. The blaOXA−23 gene appears to be widely disseminated.

Background The 2023 IDSA guidance on the Treatment of Antimicrobial Resistant Gram-negative Infections recommends combination therapy with ampicillin/sulbactam (Amp/S) for carbapenem-resistant Acinetobacter baumannii (CRAB) infections. The study purpose is to describe the prescribing patterns of Amp/S combination therapy versus monotherapy therapy for the treatment of CRAB infections. The primary endpoint of treatment failure is a composite of a change in therapy due to clinical worsening, persistent infection at 14-days, or attributable mortality from invasive infection. Secondary objectives are to evaluate outcome measures. Baseline Characteristics Patients well-matched with the exception of ICU level of care, where the combination therapy group was increased. Methods This IRB-approved, retrospective observational chart review evaluated those admitted at a Northwell Health with a culture (blood, urine, wound, lower respiratory tract) positive with CRAB. Adult patients were included if they received at least 72 hours of Amp/S monotherapy or in combination with other agents from 1/2017 to 12/2023. Patients were excluded if they expired/discharged within 72 hours of treatment. Data collected included demographics, treatment received (agents, doses, duration) and hospital length of stay (LOS). Descriptive statistics were utilized. Outcomes - Primary and Secondary Outcomes Treatment failure was seen more in the combination therapy group, which was driven by attributable mortality from invasive disease. There was no difference between the groups in terms of hospital length of stay or duration of antimicrobial therapy. Results A total of 295 patients were screened, of which 38 were included in the study. Blood cultures were most prevalent in 39.5%, followed by wound (31.6%). Most received monotherapy (57.9%) while 42.1% had combination therapy. Combination therapy was used more often when the isolate was non-susceptible (83.3% vs.to 5% when sensitive). More patients received standard compared to high-dose Amp/S (31.7% vs. 68.4% respectively). Duration of therapy was similar. One patient on monotherapy was escalated to combination of therapy. Treatment failure was seen in 9 patients in the combination therapy. The median LOS was greater in the combination therapy than monotherapy (21.5 vs. 13 days). Results - Primary and Secondary Outcomes More patients receiving high dose ampicillin/sulbactam were treated with combination therapy. More treatment failure was seen in the high-dose ampicilin/sulbactam group, but that may be due to selection bias (e.g., more critically ill patients received more aggressive therapy using combinations of antibiotics). Conclusion The prescribing patterns at Northwell Health for CRAB infections are varied and do not adhere to the IDSA guidance for CRAB infections. Most of the patients in the combination therapy had longer LOS, which may be due to selection bias in terms of disease severity. Education regarding the IDSA guidance may help steer prescribers to utilize more combination therapy with higher doses of Amp/S, Subgroup Analysis of Susceptible vs. Non-susceptible Isolates More patients with non-susceptible isolates received combination therapy. Disclosures All Authors: No reported disclosures

Preoptimized phage cocktail for use in aerosols against nosocomial transmission of carbapenem-resistant Acinetobacter baumannii: A 3-year prospective intervention study