Acinetobacter Baumannii Infections Research Articles

Laboratory Surveillance of Acinetobacter spp. Bloodstream Infections in a Tertiary University Hospital during a 9-Year Period.

Multidrug-resistant Acinetobacter baumannii infections have become a threat for public health worldwide. The aim of the present study was to follow-up resistance patterns of Acinetobacter spp. bloodstream isolates in a Tertiary University Hospital over the last nine years, from 2014 to 2022. Susceptibility patterns were followed for the following antimicrobial agents: amikacin, gentamicin, tobramycin, ciprofloxacin, levofloxacin, imipenem, meropenem, tigecycline, trimethoprim/sulfamethoxazole, and colistin. Minimal inhibitory concentration (MIC) values to ampicillin/sulbactam, cefepime, ceftazidime, minocycline, piperacillin/tazobactam were evaluated from 2020 to 2023. During the study period, 853 Acinetobacter spp. bloodstream infections (BSIs) were recorded, accounting for 5.36% of all BSIs. A. baumannii was isolated in 795 cases (93.2%), during the study period. Most BSIs were recorded in adult intensive care units (ICU) (46.2%) and medical wards (42%). Among A. baumannii isolates, 4.5% were multidrug-resistant, 84.7% were extensively drug-resistant, and 8.5% were pandrug-resistant. Resistance to carbapenems was over 95%. Resistance to tigecycline increased significantly during the last years of the study (2020-2022); A. baumannii isolates with MIC ≤ 2 μg/mL accounted for 28.5% of all isolates. Resistance to colistin exhibited an increasing pattern up to 42.2% in 2022. Increasing resistance rates and the evolution of pandrug-resistant isolates call for the urgent application of preventive and response actions.

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.

Bacteriophages and their derived enzymes as promising alternatives for the treatment of Acinetobacter baumannii infections.

Nosocomial infections with the opportunistic bacterium Acinetobacter baumannii pose a severe challenge to clinical treatment, which is aggravated by the increasing occurrence of multi-drug resistance, especially resistance to carbapenems. The use of phage therapy as an alternative and supplement to the current antibiotics has become an important research topic in the post-antibiotic era. This review summarizes in vivo and in vitro studies on phage therapy against multi-drug-resistant A. baumannii infection that have used different approaches, including treatment with a single phage, combination with other phages or non-phage agents, and administration of phage-derived enzymes. We also briefly discuss the current challenges of phage-based therapy as well as promising approaches for the treatment of A. baumannii infection in the future.

Yinhuapinggan granule ameliorates lung injury caused by multidrug-resistant Acinetobacter baumannii via inhibiting NF-κB/NLRP3 pathway

Yinhuapinggan granule (YHPG) is a traditional Chinese medicine prescription with rich clinical experience for the treatment of colds and coughs. The aim of this study is to investigate the protective effect of YHPG on multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infection in vivo and its potential anti-inflammatory mechanism. BALB/c mice were intranasally inoculated with MDR A. baumannii strain to establish the pneumonia infection model, and received intraperitoneally cyclophosphamide to form immunosuppression before attack. YHPG (6, 12 and 18 g/kg) was administered by gavage once a day for 3 consecutive days after infection. The protective effect of YHPG was evaluated by lung index, spleen index, thymus index, pathological changes of lung tissue and inflammatory factors (IL-1β, IL-6 and TNF-α) in serum. The expression of key targets of NF-κB/NLRP3 signaling pathway in vivo was analyzed by immunohistochemistry, immunofluorescence, reverse transcription quantitative PCR (RT-qPCR) and Western blot. The results showed that YHPG improved the lung index and its inhibition rate, immune organ indexes and lung pathological changes in infected mice, and significantly reduced IL-1β, IL-6 and TNF-α levels in serum. In addition, YHPG significantly down-regulated the mRNA and protein expression of NF-κB p65, NLRP3, ASC, Caspase-1, TNF-α, IL-6 and IL-1β in mice lung tissue. The results of the current study demonstrated that YHPG has significant protective effects on mice infected with MDR A.baumannii, which may be related to the regulation of inflammatory factors and NF-κB/NLRP3 signaling pathway, indicating that YHPG has a wide range of clinical application value and provides a theoretical basis for its treatment of MDR A.baumannii infection.

Antibiogram of Acinetobacter baumannii isolated from Intensive Care Unit at Prof. dr. I.G.N.G. Ngoerah Hospital in 2020-2022

Background: Acinetobacter baumannii infection is a severe problem since it tends to be multi-resistant to many antibiotics. This study aimed to determine the prevalence of A. baumannii isolated from blood, urine, and sputum cultures and their antibiotic resistance patterns. Methods: Data of A. baumanii isolated from clinical specimens of Intensive Care Unit (ICU) wards patients were collected retrospectively from laboratory records in the Clinical Microbiology Department of Prof. Dr. I. G. N. G. Ngoerah General Hospital during 2020-2022. Identification and antimicrobial susceptibility tests were conducted using the Vitek-2 Compact system (bioMérieux, France). Isolates resistant to ≥ 3 antibiotic classes were categorized as multidrug-resistant (MDR) A. baumanii. Results: A. baumanii collected from sputum, blood, and urine in Intensive Care Unit (ICU) wards were 63%, 13%, and 7.5% from 2020 until 2022. Most A. baumanii isolates in 2020, 2021, and 2022 were susceptible to Amikacin, which was 75%, 78%, and 76%, respectively. Furthermore, the isolates that were susceptible to Trimethoprim/Sulfamethoxazole were 66%, 81%, and 72%, followed by Tigecycline, 80%, 61%, and 56% respectively. A. baumanii, however, showed low sensitivity to Meropenem even though susceptibility is getting higher each year. Almost all the isolates were resistant to ceftriaxone. Conclusions: Acinetobacter baumannii isolates isolated during 2020-2022 showed high resistance to penicillin, cephalosporin and fluoroquinolones. Although A. baumanii was resistant to carbapenem, its susceptibility tends to increase throughout the 3 years of this study. These data could be considered for empirical therapy of A. baumanii infections.

Carbapenem-resistant Acinetobacter baumannii infections: Antimicrobial resistance patterns and risk factors for acquisition in a Kenyan intensive care unit

ObjectivesMultidrug-resistant (MDR) Acinetobacter baumannii (AB), especially carbapenem-resistant (CR) strains, presents a significant challenge in intensive care units (ICUs) but surveillance data in many resource-constrained countries is inadequate. Here, we determined the prevalence of MDRAB and risk factors for infection and mortality in ICU-admitted patients. MethodsA cross-sectional study among 132 consecutive patients between July 2019 and July 2020, with infected patients followed for 30 days from sample collection to ICU discharge/death. Blood, urine, and tracheal aspirate samples were processed following the standard bacteriological procedures. Isolate identity and antimicrobial susceptibility were elucidated by VITEK 2 Compact system. ResultsThe prevalence of MDRAB was 22.7% (30/132), mostly from urine samples (12.1%, 16/132), and dominated by CRAB (83.3%) that were colistin-nonresistant and exhibited high multiple antibiotic resistance indices, ranging from 0.64-0.91. Risk factors for infection were occupation (adjusted odds ratio = 4.41, P = 0.016) and interhospital referral status (adjusted odds ratio = 0.14, P = 0.001). ICU mortality was 20% (6/30). ConclusionOur findings underpin the need for strict adherence to and evaluation of infection prevention and control, and continuous surveillance of CRAB in ICU, especially among the risk groups, in the current study setting and beyond.

Multifunctional Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9-Based Nanobomb against Carbapenem-Resistant Acinetobacter baumannii Infection through Cascade Reaction and Amplification Synergistic Effect.

Carbapenems have been considered to be the preferred antibiotics against Acinetobacter baumannii thus far. However, carbapenem-resistant Acinetobacter baumannii (CRAB) has gradually escalated worldwide, and it frequently causes respiratory and bloodstream infections. Its resistance may lead to high mortality. Thus, there is an urgent need to develop antibacterial drugs. In our research, the pH-sensitive sgRNA-I/L@ZS nanosystem delivered imipenem and better released it in infected tissues to synergistically damage bacteria with nanoparticles. Gene editing of the CRISPR-Cas9 nanosystem amplified the synergistic effect by reversing the drug-resistance of imipenem. Nitric oxide, which l-arginine reacted with ROS to produce in cascade reaction and bacterial infection sites, was beneficial to heal the infected tissues and induce bacteria death for further enhancing antibacterial effects. In addition, this nanocomposite influenced host-bacteria interactions and restrained and destroyed biofilms. The sgRNA-I/L@ZS nanosystem, similar to a nanobomb, was a high-efficiency bactericide against CRAB. Eventually, in acute pneumonia and peritonitis mouse models, the sgRNA-I/L@ZS nanosystem could combat bacteria and protect tissues from infection. It had marked suppressive effects on inflammation and promoted healing and proliferation of infected tissues. This multifunctional nanosystem is expected to be an effective antibacterial agent in the clinic based on good biocompatibility and no toxic side effects. Therefore, developing the nanocomposites will take a favorable step toward solving intractable public health issues.

Synergistic Peptide-Antibiotic Approach to Combat Multidrug-Resistant Acinetobacter baumannii

Background: Antibacterial peptides have a broad antibacterial spectrum and are not affected by classical resistance mechanisms; therefore, they can be used in combination with classic antibiotics to treat multidrug-resistant Acinetobacter baumannii infections, making them an alternative for the development of new therapeutic strategies. Objectives: This study aimed to assess the effectiveness of combining amphiphilic peptides, specifically C12-prp and mastoparan, with antibiotics in combating A. baumannii clinical isolates. Methods: We investigated combinations that inhibited the growth of A. baumannii clinical isolates, consisting of 24 extensively drug-resistant (XDR) and 11 pan-drug-resistant (PDR) strains collected between January 2004 and December 2014 at Chosun University Hospital using a multiple combination bactericidal test (MCBT). A time-kill study was used to confirm the bactericidal activity and synergism of the four combinations selected via MCBT. Results: Four combinations (C12-prp-colistin, C12-prp-rifampicin, mastoparan-colistin, and mastoparan-rifampicin) showed 100% (24/24) synergy with XDR A. baumannii strains. However, in the case of the PDR strains, only two combinations, C12-prp-colistin and mastoparan-colistin, showed a 9.1% (1/11) synergy. Moreover, the mastoparan-colistin and mastoparan-rifampicin combinations showed 100% (24/24) bactericidal activity against the XDR A. baumannii strains, whereas the C12-prp-colistin and C12-prp-rifampicin combinations showed 91.7% (22/24) bactericidal activity. None of the combinations showed bactericidal activity against PDR strains. Conclusions: Our study highlighted the substantial synergistic antibacterial efficacy of C12-prp and mastoparan peptides when combined with colistin or rifampicin. Furthermore, this approach could be a promising alternative for developing new treatment strategies for XDR A. baumannii infections.

BPI23-Fcγ alleviates lethal multi-drug-resistant Acinetobacter baumannii infection by enhancing bactericidal activity and orchestrating neutrophil function

Antibiotic resistance has become a major threat, contributing significantly to morbidity and mortality globally. Administering non-antibiotic therapy, such as antimicrobial peptides, is one potential strategy for effective treatment of multi-drug-resistant Gram-negative bacterial infections. Bactericidal/permeability-increasing protein (BPI) derived from neutrophils has bactericidal and endotoxin-neutralizing activity. However, the protective roles and mechanisms of BPI in multi-drug-resistant bacterial infections have not been fully elucidated. In this study, a chimeric BPI23-Fcγ recombined protein comprising the functional N terminus of BPI and Fcγ was constructed and expressed by adenovirus vector 5 (Ad5). Ad5-BPI23-Fcγ or recombinant BPI23-Fcγ protein significantly improved the survival of mice with pneumonia induced by a minimal lethal dose of multi-drug-resistant Acinetobacter baumannii or Klebsiella pneumoniae by ameliorating lung pathology and reducing pro-inflammatory cytokines. Transfection with Ad5-BPI23-Fcγ significantly decreased the bacterial load and endotoxaemia,which was associated with enhanced bactericidal ability and elevated the phagocytic activity of neutrophils in vitro and in vivo. In addition, Ad5-BPI23-Fcγ transfection significantly increased the recruitment of neutrophils to lung, increased the proportion and number of neutrophils in peripheral blood, and promoted the maturation of bone marrow (BM) neutrophils after drug-resistant A. baumannii infection. BPI23-Fcγ and neutrophils synergistically enhanced bactericidal activity and decreased pro-inflammatory cytokines. These results demonstrated that the chimeric BPI23-Fcγ protein protected mice from pneumonia induced by multi-drug-resistant A. baumannii infection by direct bactericidal effects and promotion of neutrophil recruitment, phagocytosis and maturation. Chimeric BPI23-Fcγ may be a promising candidate as a non-antibiotic biological agent for multi-drug-resistant A. baumannii infection.

Sulbactam-Durlobactam in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Infections.

To review the pharmacology, efficacy, and safety of intravenous sulbactam-durlobactam (SUL-DUR) in the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) infections. PubMed databases and ClinicalTrials.gov were searched using the following terms: Sulbactam Durlobactam, ETX2514, Xacduro, Sulbactam-ETX2514, ETX2514SUL. Articles published in English between January 1985 and September 13, 2023, related to pharmacology, safety, efficacy, and clinical trials were reviewed. A phase II trial compared SUL-DUR with placebo with imipenem and cilastatin in both groups. Overall treatment success in the microbiological intention-to-treat analysis was reported in 76.6% of patients in the SUL-DUR group compared with 81% patients in the placebo group. A phase III trial compared SUL-DUR with colistin in adults with confirmed CRAB infections. Patients received either SUL-DUR or colistin and background therapy with imipenem-cilastatin. SUL-DUR was noninferior to colistin for 28-day all-cause mortality (19% vs 32.3%, treatment difference -13.2%; 95% CI [-30.0 to 3.5]). Clinicians have limited options to treat CRAB infections. SUL-DUR has demonstrated efficacy against CRAB in patients with pneumonia and may be considered a viable treatment option. Nonetheless, potential impact of concomitant imipenem-cilastatin as background therapy on clinical trial findings is unclear. Further studies are needed to elucidate the role of SUL-DUR alone or in combination with other active antimicrobials for the treatment of CRAB infections. SUL-DUR has shown to be predominantly noninferior to alternative antibiotics in the treatment of pneumonias caused by CRAB, making it a viable treatment option. Further postmarketing data is needed to ascertain its role in other infections.

Cefiderocol use for the treatment of infections by carbapenem-resistant Gram-negative bacteria: an Italian multicentre real-life experience.

Cefiderocol is a novel siderophore cephalosporin with promising activity against most carbapenem-resistant Gram-negative bacteria (CRGNB). However, extensive postmarketing experiences are lacking. This study aimed to analyse the early experience on cefiderocol postmarketing use at three tertiary care hospitals in Italy. We retrospectively included patients with infections caused by CRGNB treated with cefiderocol at three Italian tertiary care hospitals from 1 March 2021 to 30 June 2022. A multivariate Cox model was used to identify predictors of 30 day mortality. A propensity score (PS) analysis with inverse probability weighting (IPW) was also performed to compare the treatment effect of cefiderocol monotherapy (CM) versus combination regimens (CCRs). The cohort included 142 patients (72% male, median age 67 years, with 89 cases of Acinetobacter baumannii infection, 22 cases of Klebsiella pneumoniae, 27 cases of Pseudomonas aeruginosa and 4 of other pathogens). The 30 day all-cause mortality was 37% (52/142). We found no association between bacterial species and mortality. In multivariate analysis, a Charlson Comorbidity Index >3 was an independent predictor of mortality (HR 5.02, 95% CI 2.37-10.66, P < 0.001). In contrast, polymicrobial infection (HR 0.41, 95% CI 0.21-0.82, P < 0.05) was associated with lower mortality. There was no significant difference in mortality between patients receiving CM (n = 70) and those receiving a CCR (n = 72) (33% versus 40%, respectively), even when adjusted for IPW-PS (HR 1.11, 95% CI 0.63-1.96, P = 0.71). Real-life data confirm that cefiderocol is a promising option against carbapenem-resistant Gram-negative infections, even as monotherapy.

A cross-sectional study in critically ill patients affected by COVID-19 in an intensive care unit: would Acinetobacter baumannii resistant to carbapenems be the biggest villain?

to describe cases of infection of Acinetobacter baumannii (A. baumannii) in critically ill patients affected by COVID-19, admitted to an intensive care unit (ICU), using dexamethasone. cross-sectional study conducted on patients admitted to the intensive care unit COVID-19 survey among hospitalized patients from November 2020 to March 2021. large hospital, reference for caring for patients with COVID-19 in Bahia (Brazil). a convenience sample of 22 patients admitted to the COVID ICU signed the consent form agreeing to participate in the study. Three patients were excluded for having decided to participate without signing the form. of the 22 patients listed, 45 % (10) had blood infection or mechanical ventilation-associated pneumonia by A. baumannii in blood cultures and/or tracheal aspirate secretion. We observed that there is a moderate correlation between the length of stay and infection by A. baumannii (Spearman's ρ; 0.592; p-value<0.005) and a strong correlation between the number of days on mechanical ventilation and infection by these bacteria (Spearman's ρ; 0.740; p-value<0.001). This percentage is higher than the value of 0.62 % of infection by A. baumannii in this ICU in the same period of the year before COVID-19 (p-value<0.0001). hospitals that receive patients with COVID-19 may be vulnerable to outbreaks of multi-drug resistant organisms, such as A. baumannii . It is worth reflecting on the care and operational practices in handling these patients, especially in isolation and restriction measures for those from other nosocomial areas.

Initial indicators for the prognosis of Acinetobacter Baumannii bacteremia in children

BackgroundRisk factors related to mortality due to Acinetobacter baumannii (AB) bacteremia have been unveiled previously, but early clinical manifestations of AB bacteremia based on prognosis remain uncovered.MethodsThe demographic characteristics, clinical features, antibiotic susceptibility, and outcomes of 37 hospitalized children with laboratory-confirmed AB bacteremia from Suzhou, China, were collected and analyzed retrospectively.ResultsOf the 37 children with AB bacteremia included in this study, 23 were males and 14 were females, with a median age of 4.83 (0.60 to 10.15) years. Among the children, 18 died (48.65%, 18/37) and 19 survived (51.35%, 19/37). The dead group had a significantly higher incidence of respiratory failure (p = 0.008), shock (P = 0.000), MODS (p = 0.000), neutropenia (< 1.5 × 109/L) (p = 0.000) and serious neutropenia (< 0.5 × 109/L) (p = 0.000) than those in the survival group. The death group had significantly more invasive procedures (2 or more) than that in the survival group at 2 weeks before onset (p = 0.005). The proportion of MDR-AB in the death group was significantly higher than that in the survival group (p = 0.000), while the PICS score was significantly lower in the survival group than that in the death group (p = 0.000). There was no significant difference in effective antibiotic use within 24 h between these two groups (p = 0.295). Among the 37 children with bloodstream infection of AB, 56.76% (21/37) of the underlying diseases were hematological diseases and oncology. Among them, 17 (81.00%) were died in the hospital. The proportion of white blood cells (p = 0.000), neutrophils (p = 0.042), eosinophils (p = 0.029), the ANC (p = 0.000) and lymphocyte (p = 0.000), the NLR(p = 0.011), hemoglobin (p = 0.001), platelets (p = 0.000), prealbumin (P = 0.000), LDH (p = 0.017), blood gas pH (p = 0.000), and serum potassium (p = 0.002) in the death group were significantly lower than those in the survival group. However, CRP (p = 0.000) and blood glucose(p = 0.036) were significantly higher in the death group than those in the survival group. By further multivariate analysis, CRP [OR (95% CI): 1.022(1.003, 1.041), p = 0.021] and neutropenia [OR (95% CI): 21.634 (2.05, 228.313, p = 0.011] within 24 h of infection were independent risk factors for death in children with AB bacteremia. When CRP was higher than 59.02 mg/L, the sensitivity of predicting mortality was 88.9%, and the specificity was 78.9%. And the sensitivity and specificity of neutropenia for predicting mortality were 83.3% and 84.2%.ConclusionsAB bacteremia has a high mortality in children, especially in patients with hematological diseases and oncology. Many early indicators were associated with poor prognosis, while elevated CRP and neutropenia were the independent predictors for the 30-day mortality of children with laboratory-confirmed AB bacteremia.

How to treat severe Acinetobacter baumannii infections.

To update the management of severe Acinetobacter baumannii infections (ABI), particularly those caused by multi-resistant isolates. The in vitro activity of the various antimicrobial agents potentially helpful in treating ABI is highly variable and has progressively decreased for many of them, limiting current therapeutic options. The combination of more than one drug is still advisable in most circumstances. Ideally, two active first-line drugs should be used. Alternatively, a first-line and a second-line drug and, if this is not possible, two or more second-line drugs in combination. The emergence of new agents such as Cefiderocol, the combination of Sulbactam and Durlobactam, and the new Tetracyclines offer therapeutic options that need to be supported by clinical evidence. The apparent limitations in treating infections caused by this bacterium, the rapid development of resistance, and the serious underlying situation in most cases invite the search for alternatives to antibiotic treatment, the most promising of which seems to be bacteriophage therapy.

What is the clinical significance of 'heteroresistance' in non-fermenting Gram-negative strains?

The aim of this study was to discuss the potential clinical significance of heteroresistance in non-fermenting Gram-negative bacilli (GNB). Recently, heteroresistance has been considered potentially responsible for clinical failure in Acinetobacter baumannii infections. This raised a scientific debate, still open, about the potential clinical significance of heteroresistance in non-fermenting GNB. We reviewed the literature of last 20 years and found a limited number of studies evaluating the relationship between heteroresistance and clinical outcome in non-fermenting GNB. Unlike Gram-positive bacteria, heteroresistance is reported in a significant proportion of non-fermenting GNB with some studies describing it in all tested strains and for several antibiotics (including tigecycline, carbapenems, levofloxacin, cefiderocol, colistin). One important issue is the need for validated detection method since the population analysis profile test, that is considered the gold standard, requires high costs and time. Studies evaluating the correlation between heteroresistance and clinical outcome are contrasting and have several limitations. Although in-vitro detection of heteroresistance in non-fermenting GNB has not been associated with in-vivo treatment failure, its presence may suggest to prefer combination regimens instead monotherapy when treating infections by nonfermenters. Further studies are needed to clarify the clinical significance of heteroresistance.

An Update on the Therapeutic Potential of Antimicrobial Peptides against Acinetobacter baumannii Infections.

The rise in antibiotic-resistant strains of clinically important pathogens is a major threat to global health. The World Health Organization (WHO) has recognized the urgent need to develop alternative treatments to address the growing list of priority pathogens. Antimicrobial peptides (AMPs) rank among the suggested options with proven activity and high potential to be developed into effective drugs. Many AMPs are naturally produced by living organisms protecting the host against pathogens as a part of their innate immunity. Mechanisms associated with AMP actions include cell membrane disruption, cell wall weakening, protein synthesis inhibition, and interference in nucleic acid dynamics, inducing apoptosis and necrosis. Acinetobacter baumannii is a critical pathogen, as severe clinical implications have developed from isolates resistant to current antibiotic treatments and conventional control procedures, such as UV light, disinfectants, and drying. Here, we review the natural AMPs representing primary candidates for new anti-A. baumannii drugs in post-antibiotic-era and present computational tools to develop the next generation of AMPs with greater microbicidal activity and reduced toxicity.

Excess mortality and long-term disability from healthcare-associated carbapenem-resistant Acinetobacter baumannii infections: A nationwide population-based matched cohort study.

Carbapenem resistance is perceived as a clinical challenge in the management of debilitated and immunocompromised patients who eventually will die from underlying diseases. We aimed to examine whether carbapenem resistance per se, rather than the underlying diseases, negatively affect outcomes, by comparing the excess mortality and morbidity from healthcare-associated infections (HAIs) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-susceptible A. baumannii (CSAB). This was a nationwide retrospective matched cohort study of hospitalized patients in 96 hospitals which participated in Taiwan Nosocomial Infection Surveillance (TNIS). A total of 2,213 patients with A. baumannii HAIs were individually matched to 4,426 patients without HAIs. Main outcomes were excess risks for one-year all-cause mortality and one-year new-onset chronic ventilator dependence or dialysis-dependent end-stage renal disease. Excess one-year mortality was 27.2% in CRAB patients, compared with their matched uninfected inpatients, as well as 15.4% in CSAB patients (also compared with their matched uninfected inpatients), resulting in an attributable mortality of 11.8% (P <0.001) associated with carbapenem resistance. The excess risk associated with carbapenem resistance for new-onset chronic ventilator dependence was 5.2% (P <0.001). Carbapenem resistance was also associated with an extra cost of $2,511 per case of A. baumannii HAIs (P <0.001). Carbapenem resistance is associated with a significant disease burden in terms of excess mortality, long-term ventilator dependence, and medical cost. Further studies on effects of antimicrobial stewardship programs in decreasing this burden are warranted.

Risk factors for acquiring Acinetobacter baumannii infection in the intensive care unit: experience from a Moroccan hospital.

Acinetobacter species are non-fermenting and ubiquitous Gram-negative coccobacilli, which in recent years have become the leading cause of healthcare-associated infections worldwide. Our objective here was to study the epidemiology and risk factors associated with Acinetobacter baumannii infections in the intensive care unit (ICU). This retrospective case-control study was conducted collaboratively between the Medical Bacteriology Department and the two ICUs of the Military Hospital of Instruction Mohammed V-Rabat over a 3 month period. We included 180 patients, of whom 60 had A. baumannii infection. We observed a male predominance in both matched groups, with a sex ratio of 1.6. The median age was 67 years [interquartile range (IQR) 59.5-77]. The median length of stay in the ICU before infection was 8.5 days (IQR 5-14). Multivariate logistic regression analysis identified the risk factors statistically associated with A. baumannii infection at the ICU level as follows: duration of invasive procedures >7 days [odds ratio (OR)=1.02], parenteral nutrition (OR=3.514), mechanical ventilation (OR=3.024), imipenem (OR=18.72), colistin (OR=5.645), probabilistic antibiotic therapy >4 days (OR=9.063) and neoplastic pathology (OR=5.727). Based on our results, it can be inferred that shortening the duration of stay in the resuscitation setting, implementing rational use of medical devices and optimizing antibiotic therapy could decrease the incidence of these infections.

Enhanced immunoprotection against Acinetobacter baumannii infection: Synergistic effects of Bap and BauA in a murine model

BackgroundThe rise of multi-drug resistant Acinetobacter baumannii poses a grave threat to hospital settings, resulting in increased mortality rates and garnering global attention. The formation of biofilms facilitated by biofilm-associated protein (Bap) and the iron absorption capabilities mediated by Baumannii acinetobactin utilization A (BauA) contribute to the persistence and survival of multidrug-resistant strains. In this study, we aimed to investigate the potential of disrupting the function of BauA and Bap simultaneously as a strategy for controlling A. baumannii. MethodsRecombinant Bap and BauA were expressed, purified, and subcutaneously administered individually and in combination to BALB/c mice. Subsequently, mice were intraperitoneally challenged with A. baumannii, and the bacterial load and tissue damage in the spleen, lung, and liver were assessed. Serum samples were evaluated to determine antibody titers in surviving mice. ResultsSpecific IgG antibodies were significantly increased. A combination of the antigens resulted in enhanced titer of specific IgGs in comparison to either BauA or Bap alone. The antibodies remained stable over a seven-month period. The combination of Bap and BauA exhibited superior immunoprotection against A. baumannii infection compared to individual administration, resulting in a further reduction in bacterial load in the liver, spleen, and lungs. The histopathological analysis demonstrated successful protection of the tissues against A. baumannii-induced damage upon administration of the two immunogens. ConclusionsThe combination of Bap and BauA has the potential to target a broader range of A. baumannii strains, including those expressing either Bap or BauA, thereby increasing its efficacy against a diverse array of strains.

UTILITY OF STREM-1 BIOMARKER AND HCP GENE FOR IDENTIFICATION OF ACINETOBACTER BAUMANNII COLONIZATION AND INFECTION IN LUNG.

Objective: Respiratory infections or colonization of Acinetobacter baumannii (Ab) are common in clinical practice but are treated differently. Early identification of Ab infection and colonization reduces the risk of antibiotic mismatch but objective laboratory indicators to distinguish between bacterial infections and colonization are lacking. To distinguish infection and colonization of Ab, we tested the role of two biomarkers, triggering receptor expressed on myeloid cells-1 (TREM-1) and hemolysin coregulated protein. Methods: A total of 96 inpatients with Ab were divided into infection and colonization groups. Blood samples were collected on days 1, 2, 3, 5, 8, and 10 and daily maximum body temperature was recorded. Polymerase Chain Reaction and Reverse Transcription Polymerase Chain Reaction were used to detect the presence and expression levels of the hcp gene in Ab clinical isolates. Results : sTREM-1 and procalcitonin (PCT) levels on days 1 to 10 and neutrophil classification (N%) on days 1 to 3 were different ( P < 0.05) in the infection group and colonization group. Receiver operating characteristic (ROC) curves showed significant differences in N% and sTREM-1 on days 2 and 3 ( P < 0.01). sTREM-1 had the highest AUC ROC on days 1, 2, and 3 of all the markers. On day 1, the ROC curve of "WBC&N%&PCT&sTREM-1" was statistically different from individual indices (white blood cell count, N%, and PCT; P < 0.05) and was equal to the ROC curve of sTREM-1 ( P > 0.05). Thirty five of 96 patients were classified as infection group and 61 as colonization group with hcp gene detection rates of 71.43% (25/35) and 31.15% (19/61), respectively. No differences in hcp gene presence and transcript levels were found between two groups ( P > 0.05). Conclusions: Dynamic monitoring of sTREM-1 and PCT is valuable in identifying Ab infection and colonization. sTREM-1 can be improved by combination with multiple biomarkers in the early stage for identification of infection and colonization. The hcp gene was more likely to be present in the infection cohort.