Baumannii Research Articles

Coexistence of seven different carbapenemase producers in a single hospital admission screening confirmed by whole-genome sequencing

ObjectiveTo molecularly characterize several extensively drug-resistant isolates from a single hospital admission screening of a war injured patient from the Ukraine. MethodsAdmission screening included swabs from skin, wounds, catheters, nasopharyngeum and rectum. Bacterial identification, antimicrobial susceptibility testing (AST) and rapid multiplex PCR assays targeting resistance genes were performed during routine diagnostics. Isolates positive by PCR had their genomes sequenced using short- and long read-platforms (MiSeq and MinION) to confirm species, identify resistance genes and plasmids and investigate clonality with core genome MLST (cgMLST). ResultsSeven Gram-negative pathogens (Acinetobacter baumannii (n=2; ST78, ST2), Klebsiella pneumoniae (n=2; ST395), Pseudomonas aeruginosa (n=1; ST1047), Escherichia coli (n=1; ST46), Enterobacter cloacae complex (n=1; ST231)) were molecularly confirmed non-identical. AST showed resistance to carbapenems (7/7 isolates) and last resort treatment options such as ceftazidime-avibactam (6/7 isolates) and cefiderocol (4/7 isolates). All isolates were colistin susceptible. Sequencing identified the E. cloacae complex as E. hormaechei subsp. xiangfangensis. Six acquired carbapenemase genes (blaIMP-1, blaNDM-1, blaOXA-48, blaNDM-5, blaOXA-23 and blaOXA-72) were detected. Both A. baumannii isolates differed in sequence type, carbapenemases and cefiderocol susceptibility. Both K. pneumoniae isolates shared sequence type and some resistance genes on an IncR plasmid but were different in cgMLST and carbapenemases (OXA-48 or NDM-1). One vancomycin-resistant Enterococcus faecium was also detected (VanA). ConclusionWar injured patients from Ukraine may carry different clones of multidrug-resistant pathogens with limited treatment options and diverse resistance genes at risk for dissemination. Infection control measures should include early molecular characterization of isolates for detection of routes of transmission.

In vitro activity of cefepime-enmetazobactam on carbapenem-resistant gram negatives

ObjectivesCefepime-enmetazobactam is a new β-lactam/βlactamase inhibitor combination with broad-spectrum activity against multidrug-resistant Enterobacterales, including extended-spectrum β-lactamase producers. This study evaluated the in vitro activity of cefepime-enmetazobactam towards a collection of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa and Acinetobacter baumannii compared to the other β-lactam/β-lactamase inhibitor combinations. MethodsThe MIC of cefepime, cefepime-enmetazobactam, ceftazidime, ceftazidime-avibactam, meropenem, meropenem-vaborbactam, imipenem, imipenem-relebactam, and ertapenem were determined by broth microdilution on 2212 CRE, including 2089 carbapenemase producers (1000 OXA-48-like, 49 KPC, 697 NDM, 180 VIM, 1 IMP, 9 IMI, and 158 multiple carbapenemases) and 123 CRE that do not produce carbapenemase received at the French National Reference Centre (from March 1, 2023 to August 31, 2023), 50 P. aeruginosa, and 30 A. baumannii. All strains were fully sequenced. ResultsWe confirmed the absence of inhibitory activity of enmetazobactam towards metallo-β-lactamases. Cefepime-enmetazobactam and ceftazidime-avibactam exhibited a similar susceptibility (96.7% vs. 99.5%, respectively) on OXA-48-producers. Cefepime-enmetazobactam exhibited 66.9% and 63.3% susceptibility for CRE non-EPC and KPC, whereas those rates rose to 96.7%/95.9%, 93.4%/95.9%, and 95.9%/98.0% for ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam, respectively. Low MICs (≤0.25 mg/L) were obtained for ceftazidime-avibactam-resistant KPC variants.Cefepime-enmetazobactam did not display a significant added value when compared with cefepime alone on Pseudomonas aeruginosa and Acinetobacter baumannii. DiscussionOXA-48 producers displayed high susceptibility to cefepime-enmetazobactam, which is similar to ceftazidime-avibactam, including for OXA-48 producers that coproduce a ceftazidime hydrolyzing enzyme (extended-spectrum β-lactamases or AmpC). In vivo experiments have to be implemented to confirm if cefepime-enmetazobactam might be a relevant alternative to ceftazidime-avibactam for the treatment of infections caused by OXA-48 producers.

Molecular Detection of Carbapenemases in Acinetobacter baumannii Strains of Portugal and Association With Sequence Types, Capsular Types, and Virulence

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important nosocomial pathogen. The capsular type (K-type) is considered a major virulence factor, contributing to the evasion of host defenses. The global spread and dissemination dynamics between K-types, sequence types (ST), antibiotic resistance genes, and virulence factors remain largely unknown in Portugal. A collection of 96 CRAB clinical samples collected between 2005 and 2019 in the northern region of Portugal were tested for antimicrobial susceptibility profile and screened by polymerase chain reaction for resistance genetic determinants. A subset of 26 representative isolates was subjected to whole-genome sequencing to assess K types, ST types, and genomic relatedness. The pathogenicity of distinct K-types was also tested using Galleria mellonella model. For the 96 CRAB isolates analyzed, high antimicrobial resistance (>90%) was observed to the carbapenems, fluoroquinolones, and miscellaneous agents. Greater antimicrobial susceptibility (∼30%-57%) was observed for aminoglycosides, particularly tobramycin, and amikacin. Genotypically, 75 strains (78.5%) carried blaOXA-23-like, 18 strains (18.8%) carried blaIMP-like, and 11 strains (14.9%) carried blaOXA-40-like carbapenem resistance genes, respectively. Associations between OXA and ST/capsular locus (KL) types were observed over the years (eg, OXA-40-like/ST46Past/KL120 and OXA-23-like/ST2Past/KL2). ST2Past of clonal complex II was present in most strains, a dominant drug-resistant lineage in the United States and Europe. KL7 was also the most prevalent KL-type (38.5%), followed by KL2 (34.6%), KL120 (23.1%), and KL9 (3.8%). Virulence assessment for different K-types in a Galleria mellonella model revealed a significantly increased virulence for KL120 when compared with KL7, KL9, and KL2. There are specific CRAB serotypes circulating in Portugal, accounting by the low diversity of acquired carbapenemase genes (OXA-23-like and OXA-40-like), ST types (ST2 and ST46) and KL types (KL2, KL7, KL9, and KL120) identified. The high prevalent of ST2, especially when associated with KL2 and blaOXA-23-like, suggest that antibiotic resistance has been driven by clonal expansion of clonal complex II. Such findings provide useful information on the diversity of multidrug-resistant bacterium that might be relevant for antibacterial interventions.

Genotypic Characterisation of Carbapenemases in Clinical Isolates of Acinetobacter baumannii in a Tertiary Care Teaching Hospital of Kerala

Background: The multidrug-resistant and carbapenem-resistant Acinetobacter baumannii strains are an increasing global concern. The primary cause of carbapenem resistance in A. baumannii is production of various beta-lactamases with versatile hydrolytic capacities. The present study investigates the prevalence of different carbapenemases among clinical isolates of carbapenem-resistant A. baumannii from a tertiary care teaching hospital in Kerala, India. Methods: Non-duplicate isolates from sputum, endotracheal aspirate, pus, urine, and blood samples were included in the study. Isolate identification and antibiotic susceptibility testing of the isolates were done using vitek 2 system. A conventional polymerase chain reaction was used to detect the carbapenemase-encoding genes in the isolates. Results: A total of the 126 isolates studied, among these 105 (83.3%) isolates were from intensive care unit patients and 21(16.6%) were from non-ICU inpatients. Most of the isolates were obtained from respiratory specimens-78(61.9%) followed by pus-33(26.2%), urine-12(9.5%) and blood- 3(2.4%). The prevalence of carbapenemase genes were as follows:blaOXA-51(n=126, 100%) blaOXA-23 (n=98, 77.7%), blaOXA-58 (n=7, 5.6%), blaNDM (n=66, 52.4%), blaIMP (n=26, 20.6%), and blaVIM (n=20, 15.9%). Among the total isolates 78 (61.9%) isolates harbored metallo-beta-lactamase genes, 47(37.3%) isolates harboured a single carbapenemase gene, while 69(54.8%) isolates harbored two or more genes. Conclusion: This study reveals a higher prevalence of metallo-beta lactamases and the co-occurrence of multiple carbapenemase genes in Carbapenem resistant A. baumannii isolates.

Intrathecal Tigecycline in the Treatment of Hospital-Acquired Meningitis: A Review of Four Cases.

Objectives: Carbapenem-resistant A. baumannii is a common cause of nosocomial meningitis, and it presents a challenge in terms of treatment because of limited therapeutic options. Intravenous tigecycline has been considered a potential salvage therapy against multi-drug-resistant Acinetobacter baumannii. However, its effectiveness is limited by its poor ability to cross the blood-brain barrier. As an alternative treatment option, intrathecal tigecycline has shown promise with its minimal side effects and high concentration in cerebrospinal fluid. Methods: In this report, we present a series of four cases infected with multi-drug-resistant A. baumannii following neurosurgery and treated with intrathecal tigecycline, including antimicrobial therapy. Results: The rate of successful microbiological response was 2 out of 3 cases (66%) in whom microbiological response could be tested anytime during the intrathecal therapy, whereas the 30-day survival rate after treatment completion was ¼ (25%). Conclusion: Although intrathecal tigecycline treatment has shown relative efficacy in achieving microbiological response, its impact on overall survival is still uncertain. Further studies involving larger groups of patients are necessary to evaluate the outcomes of intrathecal tigecycline therapy.

Colistin, doxycycline and Labetalol-meropenem combination are the most active against XDR-Carbapenem-resistant Acinetobacter baumannii: role of a novel transferrable plasmid conferring carbapenem resistance

This study aimed to evaluate the antimicrobial susceptibility and combination of a beta-blocker, labetalol (LAB) and meropenem (MEM) on Carbapenem-resistant (CR) A. baumannii clinical isolates. A total of 43 CR- A. baumannii were isolated of which 37 (86.6%) and 28 (65%) exhibited MDR and XDR phenotypes, respectively. Colistin and doxycycline still retain their activities in 93.1% and 72.1% of the isolates, respectively. Combining MEM with LAB at 0.25 mg /mL, decreased MIC values in 91.4% (32/35) however, at 0.5 mg /mL, it decreased MIC value and restored susceptibility to MEM in 100% and 91.4% of the tested isolates, respectively. A novel transferable plasmid pAcbGIM3 harboring aph-3’, blaoxa-58,blaGIM3 and blaCTX-M3 and eight mobile genetic elements were successfully isolated from a pan-drug resistant (PDR) isolate. In conclusion, LAB-MEM is a promising combination and should be clinically examined. This is the first report of a transmissible plasmid harboring blaGIM3 gene in Egypt.

Interactions between Pseudomonas aeruginosa and six opportunistic pathogens cover a broad spectrum from mutualism to antagonism.

Bacterial infections often involve more than one pathogen. While it is well established that polymicrobial infections can impact disease outcomes, we know little about how pathogens interact and affect each other's behaviour and fitness. Here, we used a microscopy approach to explore interactions between Pseudomonas aeruginosa and six human opportunistic pathogens that often co-occur in polymicrobial infections: Acinetobacter baumannii, Burkholderia cenocepacia, Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, and Staphylococcus aureus. When following growing microcolonies on agarose pads over time, we observed a broad spectrum of species-specific ecological interactions, ranging from mutualism to antagonism. For example, P. aeruginosa engaged in a mutually beneficial interaction with E. faecium but suffered from antagonism by E. coli. While we found little evidence for active directional growth towards or away from cohabitants, we observed that some pathogens increased growth in double layers in response to competition and that physical forces due to fast colony expansion had a major impact on fitness. Overall, our work provides an atlas of pathogen interactions, highlighting the diversity of potential species dynamics that may occur in polymicrobial infections. We discuss possible mechanisms driving pathogen interactions and offer predictions of how the different ecological interactions could affect virulence.

Characterization and biological activity of selenium nanoparticles biosynthesized by Yarrowia lipolytica.

In this research, biogenic selenium nanoparticles were produced by the fungi Yarrowia lipolytica, and the biological activity of its nanoparticles was studied for the first time. The electron microscopy analyses showed the production of nanoparticles were intracellular and the resulting particles were extracted and characterized by XRD, zeta potential, FESEM, EDX, FTIR spectroscopy and DLS. These analyses showed amorphous spherical nanoparticles with an average size of 110 nm and a Zeta potential of -34.51 ± 2.41 mV. Signatures of lipids and proteins were present in the capping layer of biogenic selenium nanoparticles based on FTIR spectra. The antimicrobial properties of test strains showed that Serratia marcescens, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis were inhibited at concentrations between 160 and 640 μg/mL, while the growth of Candida albicans was hindered by 80 μg/mL of biogenic selenium nanoparticles. At concentrations between 0.5 and 1.5 mg/mL of biogenic selenium nanoparticles inhibited up to 50% of biofilm formation of Klebsiella pneumonia, Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, the concentration of 20-640 μg/mL of these bioSeNPs showed antioxidant activity. Evaluating the cytotoxicity of these nanoparticles on the HUVEC and HepG2 cell lines did not show any significant toxicity within MIC concentrations of SeNPs. This defines that Y. lipolytica synthesized SeNPs have strong potential to be exploited as antimicrobial agents against pathogens of WHO concern.

Investigating the antimicrobial and antibiofilm properties of marine halophilic Bacillus species against ESKAPE pathogens.

Antimicrobial resistance (AMR), known as the "silent pandemic," is exacerbated by pathogenic bacteria's ability to form biofilms. Marine compounds hold promise for novel antibacterial drug discovery. Two isolates from preliminary saltwater environment screening demonstrated antimicrobial activity and were subsequently identified as Bacillus subtilis MTUA2 and Bacillus velezensis MTUC2. Minimum inhibitory concentrations (MICs), minimum biofilm inhibition concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs) required to prevent and/or disrupt bacterial growth and biofilm formation were established for MRSA, Staphylococcus aureus, Acinetobacter baumannii and Escherichia coli. The metabolic activity within biofilms was determined by the 2,3,5-triphenyltetrazolium chloride assay. Both Bacillus species exhibited unique antimicrobial effects, reducing MRSA and S. aureus planktonic cell growth by 50% and sessile cell growth for S. aureus and E. coli by 50% and 90%, respectively. No effect was observed against A. baumannii. Significant MBIC and MBEC values were achieved, with 99% inhibition and 90% reduction in MRSA and S. aureus biofilms. Additionally, 90% and 50% inhibition was observed in E. coli and A. baumannii biofilms, respectively, with a 50% reduction in E. coli biofilm. These findings suggest that the mode of action employed by B. subtilis MTUA2 and B. velezensis MTUC2 metabolites should be further characterized and could be beneficial if used independently or in combination with other treatments.

Investigating an Outbreak of Extensively Drug-Resistant Acinetobacter baumannii in a Tertiary Healthcare Centre in Lebanon Using Next-Generation Sequencing

The frequent occurrence of Acinetobacter baumannii in hospital settings and the elevated rate of antimicrobial resistance in this pathogen represent a serious clinical and public health threat worldwide, and particularly in Lebanon where outbreak surveillance and control are still insufficient. Whole-genome sequencing (WGS) is a fast and reliable tool to study outbreaks at the molecular level and obtain actionable knowledge, leading to better control measures. A total of 59 A. baumannii isolates were collected from intensive care unit (ICU) patients (57 isolates) and from the hospital environment (2 isolates) between August 2022 and May 2023, antimicrobial susceptibility testing (AST) was performed and gDNA was subjected to WGS. Analysis was performed to reveal the sequence types (ST), the relatedness to strains that caused other outbreaks and the arsenal of resistance genes harboured by these bacteria. Of 59 isolates, 85% were categorised as extensively drug-resistant (XDR), 13.6% as multidrug-resistant (MDR) and 1.7% as pan-drug-resistant. All isolates belonged to international clone (IC)2, of which the majority were of ST2 (91.5%). The isolates clustered well with those of a previous outbreak in the same hospital. In addition, isolates from hospitals in Lebanon clustered well together and some clustered with those originating from other countries. The observed genetic relatedness between the current isolates and those from the previous outbreaks underscores the importance of strict surveillance to limit the threat of outbreaks. Moreover, the clustering of isolates from Lebanon with others from distant countries proves the necessity to further investigate the international spread of drug-resistant pathogens and the implementation of control strategies.

Emergence of extensively drug-resistant hypervirulent Acinetobacter baumannii isolated from patients with bacteremia: bacterial phenotype and virulence analysis

ObjectivesIndividuals infected with extensively drug-resistant (XDR) Acinetobacter baumannii are difficult to cure and have a high mortality rate. In this study, we compared the genomic and phenotypic differences between XDR and non-multidrug-resistant (MDR) A. baumannii and further characterized hypervirulent XDR A. baumannii. MethodsA total of 1,403 Acinetobacter isolates were collected from patients with bacteremia between 1997 and 2015. Antimicrobial susceptibility test was performed to categorize isolates into non-MDR, MDR, and XDR groups. The presence of selected virulence-associated genes was determined by PCR. Bacterial phenotypes, including iron acquisition, biofilm formation, capsule production, and virulence to larvae and mice, were determined. ResultsMultilocus sequence types revealed the high prevalence of ST2 (81.6%) and ST129 (18.4%) among 49 XDR isolates and sequence types of 18 non-MDR isolates were more diverse. Virulence-associated phenotypic assays showed that XDR isolates had higher iron acquisition ability and capsule production and higher virulence to Galleria mellonella larvae. However, their biofilm formation ability was lower compared to that of non-MDR isolates. XDR isolates contained more virulence genes, tonB, hemO, abaI, and ptk, while non-MDR isolates contained more pld and ompA. Twenty-one XDR isolates caused <20% larvae survival rate after 7 days post-infection were defined as hypervirulent XDR isolates. Among them, isolates 1677 (ST129) and 929-1 (ST2) also caused the death of all infected mice within two days. ConclusionSome subpopulations of highly drug-resistant ST2 also exhibit high virulence. Therefore, it is of utmost importance to continue monitoring the spread of hypervirulent XDR A. baumannii isolates.

Navigating the Current Treatment Landscape of Metallo-β-Lactamase-Producing Gram-Negative Infections: What are the Limitations?

The spread of carbapenemase-producing gram-negative pathogens, especially those producing metallo-β-lactamases (MBLs), has become a major health concern. MBLs are molecularly the most diverse carbapenemases, produced by a wide spectrum of gram-negative organisms, including the Enterobacterales, Pseudomonas spp., Acinetobacter baumannii, and Stenotrophomonas maltophilia, and can hydrolyze most β-lactams using metal ion cofactors in their active sites. Over the years, the prevalence of MBL-carrying isolates has increased globally, particularly in Asia. MBL infections are associated with adverse clinical outcomes including longer length of hospital stay, ICU admission, and increased mortality across the globe. The optimal treatment for MBL infections not only depends on the pathogen but also on the underlying resistance mechanisms. Currently, there are only few drugs or drug combinations that can efficiently offset MBL-mediated resistance, which makes the treatment of MBL infections challenging. The rising concern of MBLs along with the limited treatment options has led to the need and development of drugs that are specifically targeted towards MBLs. This review discusses the prevalence of MBLs, their clinical impact, and the current treatment options for MBL infections and their limitations. Furthermore, this review will discuss agents currently in the pipeline for treatment of MBL infections.

Development of LC-FAIMS-MS and its application to lipidomics study of Acinetobacter baumannii infection

The recent advances in mass spectrometry (MS) technologies have enabled comprehensive lipid profiling in biological samples. However, the robustness and efficiency of MS-based lipidomics is compromised by the complexity of biological samples. High-field asymmetric waveform ion mobility spectrometry (FAIMS) is a technology that can continuously transmit one type of ion, independent of the mass-to-charge ratio. Here we present the development and application of LC-FAIMS-MS/MS-based platform for untargeted lipidomics. We used 3 optimally balanced compensation voltages, i.e., 29 V, 34 V and 39 V, to analyze all subclasses of glycerophospholipids. The reproducibility of the method was evaluated using reference standards. The reproducibility of retention times ranged from 0.9% to 1.5% RSD; whereas RSD values of 5%–10% were observed for peak areas. More importantly, the coupling of a FAIMS device can significantly improve the robustness and efficiency. We exploited this NPLC-FAIMS-HRMS to analyze the serum lipid profiles in mice infected intranasally with Acinetobacter baumannii. The temporal profiles of serum lipids after A. baumannii inoculation were obtained for 4 h, 8 h, and 24 h. We found that nearly all ether PC and ether PE lipids were significantly decreased 8 h after inoculation. The resultant volcano plot illustrated the distribution of 28 increased and 28 decreased lipid species in mouse sera 24 h after inoculation. We also found that a single ether PE composition can comprise multiple isomeric structures, and the relative abundance of each isomer could be quantified using the newly developed NPLC-FAIMS-PRM method.

Comprehensive Assessment of Antioxidant, Antimicrobial, and Cytotoxic Activities of Schiff Bases Synthesized from Phenyl Glyoxal: Insights from Molecular Docking and ADMET Analysis

AbstractIn this study, novel Schiff base, PTIEO and PABHP were synthesized using Phenyl Glyoxal as a major constituent and their structures were elucidated through modern spectroscopic techniques. Antioxidant assays were performed using DPPH and ABTS assays. Further, PTIEO and PABHP were subjected to in vitro biological evaluations against ESKAP pathogens. This investigation revealed significant antibacterial activity of both compounds, with MIC below 64 μg mL−1 against Staphylococcus aureus and 64 μg mL−1 against Acinetobacter baummanii. In molecular docking studies, PTIEO shows enhanced binding energy with Acinetobacter baumannii bacterial protein Diaminopimelate epimerase at −7.45 Kcal mol−1, while PABHP exhibited −8.32 Kcal mol−1 binding energy with NADH‐dependent enoyl‐ACP reductase. Additionally, PTIEO and PABHP demonstrated good binding energy with Sortase‐A of Staphylococcus aureus at −7.59 Kcal mol−1 and −8.75 Kcal mol−1, respectively. Moreover, antifungal capabilities of these compounds were evaluated against pathogenic fungi Candida Albicans, Candida Parapsilosis, and Candida tropicalis, highlighting their broad‐spectrum antimicrobial properties. Moreover, PABHP displayed cytotoxicity with an IC50 value of 23.50 μg mL−1, suggesting its safer administration. ADMET calculations were also performed to demonstrate their effectiveness. Overall, these experiments attribute to the significant therapeutic behavior of Schiff bases as comprehensive biomedical agents.

Effectiveness and Safety of Cefiderocol in Clinical Practice for Treatment of Patients with Gram-Negative Bacterial Infections: US Interim Results of the PROVE Study.

The international PROVE retrospective chart-review study aims to assess the real-world effectiveness and safety of cefiderocol for treatment of patients with carbapenem-resistant Gram-negative infections. US centers selected hospitalized patients receiving their first cefiderocol treatment for ≥72hours for a Gram-negative bacterial infection (November 2020-March 2023). Patient demographics, clinical characteristics, hospitalization, course of infection, antibiotic use, clinical cure (excluding patients with a relapse/reinfection), clinical response at the end of treatment, microbiology, in-hospital all-cause mortality (IH-ACM) at Day 30, and safety were analyzed using descriptive statistics. This interim analysis included 244 patients. The most frequent infection sites were respiratory tract (55.7%), skin and skin structure (16.8%), and blood (9.8%). The median duration of cefiderocol use was 12 days (interquartile range 8-18.5). Clinical cure was reported for 64.8% (158/244) of patients, clinical response for 74.2% (181/244), and 9.4% (23/244) had relapse/reinfection; 30-day IH-ACM was 18.4% (45/244). Of 82 patients with monomicrobial Pseudomonas aeruginosa infections, 64.6% (n = 53) and 74.4% (n = 61) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 25.6%. Among 43 patients with monomicrobial Acinetobacter baumannii infections, 60.5% (n = 26) and 74.4% (n = 32) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 18.6%. Five patients experienced six adverse drug reactions (one serious event: interstitial nephritis/acute kidney injury), and cefiderocol was discontinued in two cases. Cefiderocol had similar clinical cure and response rates to previous retrospective studies and lower mortality. Cefiderocol was well tolerated in real-world settings in critically ill US patients with problematic Gram-negative pathogens.

Efficacy of fosfomycin-containing regimens in treating severe infections caused by KPC-producing Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii in critically ill patients

IntroductionFosfomycin (FOS) is gaining increasing importance as part of combination therapy for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) and KPC-producing Klebsiella pneumoniae (KPC-Kp) thanks to its in-vitro synergism with several antibiotics, high tissue distribution and good tolerability.We analyzed the effect on 30-day survival of FOS-containing regimens compared to NO-FOS in critically ill patients admitted to intensive care unit with CRAB or KPC-Kp infections. Secondary objectives were to evaluate clinical cure and microbiologic eradication of FOS versus NO-FOS group. Materials/methodsMonocentric retrospective observational study including SARS-Cov2-negative critically ill patients with KPC-Kp or CRAB infection treated with combination antibiotic therapy with or without FOS for ≥48h (FOS vs NO-FOS groups). Primary outcome was 30-d mortality, secondary outcomes clinical cure and microbiological eradication. ResultsOf the 78 patients analyzed, 26 (33.3%) were men, median (IQR) age and Charlson Comorbidity Index (CCI) were 67 years (53-74) and 4 (2-5), respectively. Septic shock was present in 18 patients (23.1%), 37 (47.4%) were CRAB, 41 (52.6%) KPC-Kp. Compared to NO-FOS, patients receiving FOS had higher clinical cure (89.2%vs65.9%, p=0.017), early (<72h) improvement (78.4%vs52.2%, p=0.018), microbiological eradication (87.5%vs62.2%, p=0.027) and lower 7-, 14- and 30-d mortality (0%vs4.6%, p=0.027, 2.7%vs22%, p=0.016, 13.5%vs34.2%, p=0.039, respectively). This effect was particularly evident for infections sustained by KPC-Kp. At multivariate analysis, receiving FOS was independently associated with survival (HR 0.29, IC95% 0.09-0.93, p=0.038), confirmed after IPTW (HR 0.501 IC95% 0.25-0.98 p=0.042). ConclusionsFOS-containing regimens exhibit higher clinical cure, higher microbiological eradication and reduced mortality than NO FOS-containing regimens in critically ill patients with CRAB and KPC-Kp infections.

Effect of colistin combined with sulbactam: 9 g versus 12 g per day on mortality in the treatment of carbapenems resistant Acinetobacter baumannii pneumonia: a randomized controlled trial.

The current treatment recommendation involves administering a high dose of sulbactam alongside at least one additional agent. However, there remains a lack of data regarding the optimal dosage of sulbactam. We investigated whether administering sulbactam at a dosage of 12 g/day decreases the mortality rate among patients with CRAB pneumonia compared to 9 g/day. The study was an open-label, superiority, randomized controlled trial conducted at Phramongkutklao Hospital between September 2019 and September 2023 in patients diagnosed with CRAB. Participants were randomly assigned to receive a combination of colistin with either 9 or 12 g/day of sulbactam. The primary endpoint was the all-cause mortality rate at 28 days post-randomization. Among the 138 participants, there was a trend toward a lower mortality rate in the 12 g/day group (59.4% vs. 47.8%; p = 0.158). After adjusting for factors associated with mortality, a lower mortality was observed in the 12 g/day group (adjusted HR 0.54 [95% CI 0.33-0.87]; p = 0.0110). The microbiological cure rate at day 7 was higher in the 12 g/day group (73.2% vs. 89.4%; p = 0.02). Colistin in combination with sulbactam at a dosage of 12 g/day may improve mortality compared to 9 g/day.

Optimizing Treatment Strategies for Carbapenem-Resistant Acinetobacter Baumannii-Associated Pneumonia: A Multicenter Study in Chinese Hospitals.

To evaluate the clinical outcomes and safety of tigecycline (TGC) plus cefoperazone/sulbactam (CPS) or TGC monotherapy in patients with hospital-acquired pneumonia (HAP) caused by Carbapenem-Resistant Acinetobacter baumannii (CRAB). This was a retrospective analysis of multicenter data from 62 Chinese hospitals with CRAB HAP. Risk factors for receiving TGC with CPS therapy and predictors of mortality were assessed using multivariate logistic and Cox regression analyses, respectively. Propensity score matching (PSM) evaluated the efficacy and safety of antimicrobial regimens. A total of the 180 patients were included, with 95 receiving TGC monotherapy and 85 receiving combination therapy. Multivariate logistic regression analysis revealed that older age (P = 0.011), and intensive care unit (ICU) admission (P = 0.007) were significant risk factors for combination therapy. Multivariate Cox regression demonstrated that combination therapy was associated with a significantly higher risk of 90-day mortality (P = 0.031). Patients in the standard-dose TGC (SDT) plus CPS subgroup had significantly higher rates of SOFA scores ≥ 7 (P = 0.009) and MV used (P = 0.028), as well as higher 30-/90-day mortality compared to high-dose TGC (HDT) plus CPS group. TGC plus CPS significantly reduced CRP levels (P = 0.009), while the variations in ALT, TBIL, Cr, Hb, and PLT levels did not differ between different antimicrobial regimens after PSM. HDT and CPS combination therapy was more effective in patients with advanced age and more severe condition. Safety profiles of different antimicrobial regimens were similar with liver, kidneys, and coagulation functions.

Correction: Comparison of cefiderocol and colistin-based regimens for the treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review with meta-analysis and trial sequential analysis

Correction: Comparison of cefiderocol and colistin-based regimens for the treatment of severe infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review with meta-analysis and trial sequential analysis

Elimination of an outbreak of carbapenem-resistant Acinetobacter baumannii in a burn unit

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an opportunistic pathogen which has caused numerous healthcare-associated outbreaks particularly in intensive care and burn units. We describe an outbreak in a burn unit where 3 patients were identified as being colonized or infected with CRAB. A multi-faceted approach and rapid implementation of infection prevention measures were effective in identification and removal of potential environmental reservoirs resulting in the prevention of further transmission.