Co-Occurrence of Two Plasmids Encoding Transferable blaNDM-1 and tet(Y) Genes in Carbapenem-Resistant Acinetobacter bereziniae.

Acinetobacter bereziniae has emerged as a significant human pathogen, acquiring multiple antibiotic resistance genes, including carbapenemases. This study focuses on characterizing the plasmids harboring the blaNDM-1 and tet(Y) genes in two carbapenem-resistant A. bereziniae isolates (UCO-553 and UCO-554) obtained in Chile during the COVID-19 pandemic. Methods: Antibiotic susceptibility testing was conducted on UCO-553 and UCO-554. Both isolates underwent whole-genome sequencing to ascertain their sequence type (ST), core genome multilocus sequence-typing (cgMLST) profile, antibiotic resistance genes, plasmids, and mobile genetic elements. Conjugation experiments were performed for both isolates. Results: Both isolates exhibited broad resistance, including resistance to carbapenems, third-generation cephalosporins, fluoroquinolones, tetracycline, cotrimoxazole, and aminoglycosides. Both isolates belong to sequence type STPAS1761, with a difference of 17 out of 2984 alleles. Each isolate carried a 47,274 bp plasmid with blaNDM-1 and aph(3')-VI genes and two highly similar plasmids: a 35,184 bp plasmid with tet(Y), sul2, aph(6)-Id, and aph(3″)-Ib genes, and a 6078 bp plasmid containing the ant(2″)-Ia gene. Quinolone-resistance mutations were identified in the gyrA and parC genes of both isolates. Importantly, blaNDM-1 was located within a Tn125 transposon, and tet(Y) was embedded in a Tn5393 transposon. Conjugation experiments successfully transferred blaNDM-1 and tet(Y) into the A. baumannii ATCC 19606 strain, indicating the potential for horizontal gene transfer. Conclusions: This study highlights the critical role of plasmids in disseminating resistance genes in A. bereziniae and underscores the need for the continued genomic surveillance of this emerging pathogen. The findings emphasize the importance of monitoring A. bereziniae for its potential to cause difficult-to-treat infections and its capacity to spread resistance determinants against clinically significant antibiotics.

New antibacterial candidates against Acinetobacter baumannii discovered by in silico-driven chemogenomics repurposing.

Acinetobacter baumannii is a worldwide Gram-negative bacterium with a high resistance rate, responsible for a broad spectrum of hospital-acquired infections. A computational chemogenomics framework was applied to investigate the repurposing of approved drugs to target A. baumannii. This comprehensive approach involved compiling and preparing proteomic data, identifying homologous proteins in drug-target databases, evaluating the evolutionary conservation of targets, and conducting molecular docking studies and in vitro assays. Seven drugs were selected for experimental assays. Among them, tavaborole exhibited the most promising antimicrobial activity with a minimum inhibitory concentration (MIC) value of 2 µg/ml, potent activity against several clinically relevant strains, and robust efficacy against biofilms from multidrug-resistant strains at a concentration of 16 µg/ml. Molecular docking studies elucidated the binding modes of tavaborole in the editing and active domains of leucyl-tRNA synthetase, providing insights into its structural basis for antimicrobial activity. Tavaborole shows promise as an antimicrobial agent for combating A. baumannii infections and warrants further investigation in preclinical studies.

An outbreak of severe or lethal infections by a multidrug-resistant Acinetobacter baumannii ST126 strain carrying a plasmid with blaNDM-1 and blaOXA-58 carbapenemases.

Acinetobacter baumannii poses a significant health threat because of its frequent implications in hospital outbreaks and multidrug resistance (MDR). Here, we studied four A. baumannii isolates recovered during a hospital outbreak of severe or fatal cases to elucidate their diversity and factors contributing to their increased virulence and antibiotic resistance. The isolates were identified using MALDI-ToF and characterized using comparative genomics, PCR, and antimicrobial susceptibility tests. They were classified as ST126 and exhibited fewer than five chromosomal single-nucleotide variants and the same extrachromosomal content, indicating that they are a single strain (A. baumannii AB01). A. baumannii AB01 showed an MDR phenotype that could be linked to the carriage of parC and gyrA mutations, efflux transporters, aminoglycoside resistance genes, a class C beta-lactamase, and three carbapenemases, some of which are encoded on a 72 kb plasmid. ST126 is infrequent and has not been reported in Latin America, and our genomic data indicate a plausible origin for A. baumannii AB01 within the Pan Pacific region.

Antibiofilm effect of biogenic silver nanoparticle alone and combined with polymyxin B against carbapenem-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a bacteria associated with nosocomial infections and outbreaks, difficult to control due to its antibiotic resistance, ability to survive in adverse conditions, and biofilm formation adhering to biotic and abiotic surfaces. Therefore, this study aimed to evaluate the antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) and polymyxin B alone and combined in biofilms formed by isolates of carbapenem-resistant A. baumannii (CR-Ab). In the biofilm formation inhibition assay, CR-Ab strains were exposed to different concentrations of the treatments before inducing biofilm formation, to determine the ability to inhibit/prevent bacterial biofilm formation. While in the biofilm rupture assay, the bacterial biofilm formation step was previously carried out and the adhered cells were exposed to different concentrations of the treatments to evaluate their ability to destroy the bacterial biofilm formed. All CR-Ab isolates and ATCC® 19606™ used in this study are strong biofilm formers. The antibiofilm activity of Bio-AgNP and polymyxin B against CR-Ab and ATCC® 19606™ demonstrated inhibitory and biofilm-disrupting activity. When used in combination, Bio-AgNP and polymyxin B inhibited 4.9-100% of biofilm formation in the CR-Ab isolates and ATCC® 19606™. Meanwhile, when Bio-AgNP and polymyxin B were combined, disruption of 6.8-77.8% of biofilm formed was observed. Thus, antibiofilm activity against CR-Ab was demonstrated when Bio-AgNP was used alone or in combination with polymyxin B, emerging as an alternative in the control of CR-Ab strains.

Genetic profile and characterization of antimicrobial resistance in Acinetobacter baumannii post-COVID-19 pandemic: a study in a tertiary hospital in Recife, Brazil.

AIMS: To investigate the genetic profile and characterize antimicrobial resistance, including the main ß-lactam antibiotic resistance genes, in Acinetobacterbaumannii isolates from a tertiary hospital in Recife-PE, Brazil, in the post-COVID-19 pandemic period. METHODS AND RESULTS: Acinetobacter baumannii isolates were collected between 2023 and 2024 from diverse clinical samples. Antimicrobial resistance testing followed standardized protocols, with ß-lactamase-encoding genes detected via PCR and sequencing. Investigation into ISAba1 upstream of blaOXA-carbapenemase and blaADC genes was also conducted. Genetic diversity was assessed through ERIC-PCR. Among the 78 A. baumannii, widespread resistance to multiple antimicrobials was evident. Various acquired ß-lactamase-encoding genes (blaOXA-23,-24,-58,-143, blaVIM, and blaNDM) were detected. Furthermore, this is the first report of blaVIM-2 in A. baumannii isolates harboring either the blaOXA-23-like or the blaOXA-143 gene in Brazil. Molecular typing revealed a high genetic heterogeneity among the isolates, and multi-clonal dissemination. CONCLUSION: The accumulation of genetic resistance determinants underscores the necessity for stringent infection control measures and robust antimicrobial stewardship programs to curb multidrug-resistant strains.

Evaluating virulence features of Acinetobacter baumannii resistant to polymyxin B.

The increasing resistance to polymyxins in Acinetobacter baumannii has made it even more urgent to develop new treatments. Anti-virulence compounds have been researched as a new solution. Here, we evaluated the modification of virulence features of A. baumannii after acquiring resistance to polymyxin B. The results showed lineages attaining unstable resistance to polymyxin B, except for Ab7 (A. baumannii polymyxin B resistant lineage), which showed stable resistance without an associated fitness cost. Analysis of virulence by a murine sepsis model indicated diminished virulence in Ab7 (A. baumannii polymyxin B resistant lineage) compared with Ab0 (A. baumannii polymyxin B susceptible lineage). Similarly, downregulation of virulence genes was observed by qPCR at 1 and 3 h of growth. However, an increase in bauE, abaI, and pgAB expression was observed after 6 h of growth. Comparison analysis of Ab0, Ab7, and Pseudomonas aeruginosa suggested no biofilm formation by Ab7. In general, although a decrease in virulence was observed in Ab7 when compared with Ab0, some virulence feature that enables infection could be maintained. In light of this, virulence genes bauE, abaI, and pgAB showed a potential relevance in the maintenance of virulence in polymyxin B-resistant strains, making them promising anti-virulence targets.

Comparison of available methods to evaluate cefiderocol susceptibility in Acinetobacter spp.

Recently, considerable uncertainty has arisen concerning the appropriate susceptibility testing for cefiderocol in gram-negative bacilli, particularly in the context of its application to Acinetobacter spp. The optimal method for assessing the susceptibility levels of Acinetobacter spp. to cefiderocol remains a subject of debate due to substantial disparities observed in the values obtained through various testing procedures. This study employed four minimum inhibitory concentration (MIC) methodologies and the disk diffusion to assess the susceptibility of twenty-seven carbapenem resistant (CR)-Acinetobacter strains to cefiderocol. The results from our study reveal significant variations in the minimum inhibitory concentration (MIC) values obtained with the different methods and in the level of agreement in interpretation categories between the different MIC methods and the disk diffusion test. Among the MIC methods, there was relatively more consistency in reporting the interpretation categories. For European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, the categorical agreement (CA) for MIC methods ranged between 66.7 and 81.5%. On the other hand, the essential agreement (EA) values were as low as 18.5-29.6%. The CA between MIC methods and disk diffusion was 81.5%. These results emphasize the need for a reliable, accurate, and clinically validated methodology to effectively assess the susceptibility of Acinetobacter spp. to cefiderocol. The wide variability observed in our study highlights the importance of standardizing the susceptibility testing process for cefiderocol to ensure consistent and reliable results for clinical decision-making.

Hypothetical adhesin CAM87009.1 formulated in alum or biogenic silver nanoparticles protects mice from lethal infection by multidrug-resistant Acinetobacter baumannii.

Due to its antimicrobial resistance characteristics, the World Health Organization (WHO) classifies A. baumannii as one of the critical priority pathogens for the development of new therapeutic strategies. Vaccination has been approached as an interesting strategy to overcome the lack of effective antimicrobials and the long time required to develop and approve new drugs. In this study, we aimed to evaluate as a vaccine the hypothetical adhesin protein CAM87009.1 in its recombinant format (rCAM87009.1) associated with aluminum hydroxide (Alhydrogel®) or biogenic silver nanoparticles (bio-AgNP) as adjuvant components against lethal infection by A. baumannii MDR strain. Both vaccine formulations were administered in three doses intramuscularly in BALB/c murine models and the vaccinated animals were tested in a challenge assay with A. baumannii MDR strain (DL100). rCAM87009.1 protein associated with both adjuvants was able to protect 100 % of animals challenged with the lethal strain during the challenge period. After the euthanasia of the animals, no A. baumannii colonies were detected in the lungs of animals vaccinated with the rCAM87009.1 protein in both formulations. Since the first immunization, high IgG antibody titers were observed (1:819,200), with results being statistically similar in both vaccine formulations evaluated. rCAM87009.1 associated with both adjuvants was capable of inducing at least one class of isotypes associated with the processes of neutralization (IgG2b and IgA for bio-AgNP and Alhydrogel®, respectively), opsonization (IgG1 in both vaccines) and complement activation (IgM and IgG3 for bio-AgNP and Alhydrogel®, respectively). Furthermore, reduced tissue damage was observed in animals vaccinated with rCAM87009.1 + bio-AgNP when compared to animals vaccinated with Alhydrogel®. Our results indicate that the rCAM87009.1 protein associated with both bio-AgNP and Alhydrogel® are combinations capable of promoting immunity against infections caused by A. baumannii MDR. Additionally, we demonstrate the potential of silver nanoparticles as alternative adjuvant molecules to the use of aluminum salts.

Acinetobacter baumannii as an oro-dental pathogen: a red alert!!

OBJECTIVES: This review highlights the existence and association of Acinetobacter baumannii with the oro-dental diseases, transforming this systemic pathogen into an oral pathogen. The review also hypothesizes possible reasons for the categorization of this pathogen as code blue due to its stealthy entry into the oral cavity. METHODOLOGY: Study data were retrieved from various search engines reporting specifically on the association of A. baumannii in dental diseases and tray set-ups. Articles were also examined regarding obtained outcomes on A. baumannii biofilm formation, iron acquisitions, magnitude of antimicrobial resistance, and its role in the oral cancers. RESULTS: A. baumannii is associated with the oro-dental diseases and various virulence factors attribute for the establishment and progression of oro-mucosal infections. Its presence in the oral cavity is frequent in oral microbiomes, conditions of impaired host immunity, age related illnesses, and hospitalized individuals. Many sources also contribute for its prevalence in the dental health care environment and the presence of drug resistant traits is also observed. Its association with oral cancers and oral squamous cell carcinoma is also evident. CONCLUSIONS: The review calls for awareness on the emergence of A. baumannii in dental clinics and for the need for educational programs to monitor and control the sudden outbreaks of such virulent and resistant traits in the dental health care settings.

Phenotypic and molecular characterization of clinically isolated antibiotics-resistant S. aureus (MRSA), E. coli (ESBL) and Acinetobacter 1379 bacterial strains.

Antibiotic-resistant bacteria causing nosocomial infections pose a significant global health concern. This study focused on examining the lipid profiles of both non-resistant and clinically resistant strains of Staphylococcus aureus (MRSA 1418), E. coli (ESBL 1384), and Acinetobacter 1379. The main aim was to investigate the relationship between lipid profiles, hydrophobicity, and antibiotic resistance so as to identify the pathogenic potential and resistance factors of strains isolated from patients with sepsis and urinary tract infections (UTIs). The research included various tests, such as antimicrobial susceptibility assays following CLSI guidelines, biochemical tests, biofilm assays, and hydrophobicity assays. Additionally, gas chromatography mass spectrometry (GC-MS) and GC-Flame Ionization Detector (GC-FID) analysis were used for lipid profiling and composition. The clinically isolated resistant strains (MRSA-1418, ESBL-1384, and Acinetobacter 1379) demonstrated resistance phenotypes of 81.80%, 27.6%, and 63.6%, respectively, with a multiple antibiotic resistance index of 0.81, 0.27, and 0.63. Notably, the MRSA-1418 strain, which exhibited resistance, showed significantly higher levels of hemolysin, cell surface hydrophobicity, biofilm index, and a self-aggregative phenotype compared to the non-resistant strains. Gene expression analysis using quantitative real-time PCR (qPCR). Indicated elevated expression levels of intercellular adhesion biofilm-related genes (icaA, icaC, and icaD) in MRSA-1418 (pgaA, pgaC, and pgaB) and Acinetobacter 1379 after 24 h compared to non-resistant strains. Scanning electron microscopy (SEM) was employed for structural investigation. These findings provide valuable insights into the role of biofilms in antibiotic resistance and suggest potential target pathways for combating antibiotic-resistant bacteria.

Carbapenemase genes in clinical and environmental isolates of Acinetobacter spp. from Quito, Ecuador.

Carbapenem-resistant Acinetobacter spp. is associated with nosocomial infections in intensive care unit patients, resulting in high mortality. Although Acinetobacter spp. represent a serious public health problem worldwide, there are a few studies related to the presence of carbapenemases in health care facilities and other environmental settings in Ecuador. The main aim of this study was to characterize the carbapenem-resistant Acinetobacter spp. isolates obtained from four hospitals (52) and from five rivers (27) close to Quito. We used the disc diffusion and EDTA sinergy tests to determine the antimicrobial susceptibility and the production of metallo ß-lactamases, respectively. We carried out a multiplex PCR of gyrB gene and the sequencing of partial rpoB gene to bacterial species identification. We performed molecular screening of nine carbapenem-resistant genes (blaSPM, blaSIM, blaGIM, blaGES, blaOXA-23, blaOXA-24, blaOXA-51, blaOXA-58, and blaOXA-143) by multiplex PCR, followed by identification using sequencing of blaOXA genes. Our findings showed that carbapenem-resistant A. baumannii were the main species found in health care facilities and rivers. Most of the clinical isolates came from respiratory tract samples and harbored blaOXA-23, blaOXA-366, blaOXA-72, blaOXA-65, blaOXA-70, and blaOXA-143-like genes. The river isolates harbored only the blaOXA-51 and probably blaOXA-259 genes. We concluded that the most predominant type of carbapenem genes among isolates were both blaOXA-23 and blaOXA-65 among A. baumannii clinical isolates.

Antibodies anti-rFilF protein has anti-biofilm activity against carbapenem-resistant Acinetobacter baumannii.

Acinetobacter baumannii is an opportunistic bacterium that causes infection in several sites. Carbapenem-resistant A. baumannii strains (CRAb) lead the World Health Organization's list of 12 pathogens considered a priority for developing new antimicrobials. The pathogenicity of A. baumannii is related to the different virulence factors employed in the colonization of biotic and abiotic surfaces, biofilm formation and multidrug resistance. We analyze the outer membrane protein FilF from A. baumannii in silico and produce it in recombinant form (rFilF). rFilF protein was successfully expressed in Escherichia coli BL21 Star in an insoluble form. Immunization with rFilF induced significant anti-rFilF IgG antibody production in mice, detected by indirect enzyme-linked immunosorbent assay, since the first evaluation until 49th. On the last experimentation day, the predominant immunoglobulin found was IgG1 followed by IgG2a, IgG2b, IgM, IgG3, and IgA. We observe that interleukins 4 and 10 show significant production after the 28th day of experimentation in mice immunized with rFilF. Anti-rFilF pAbs were able to inhibit biofilm formation in nine CRAb strains evaluated, and in the standard strain ATCC® 19606. These results demonstrate the anti-biofilm activity of anti-rFilF antibodies, promising in the development of a non-antibiotic approach based on the control of CRAb strains.

The synergic and addictive activity of biogenic silver nanoparticle associated with meropenem against carbapenem-resistant Acinetobacter baumannii.

AIMS: Antibiotic management of infections caused by Acinetobacter baumannii often fails due to antibiotic resistance (especially to carbapenems) and biofilm-forming strains. Thus, the objective here was to evaluate in vitro the antibacterial and antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) combined with meropenem, against multidrug-resistant isolates of A. baumannii. METHODS AND RESULTS: In this study, A. baumannii ATCC® 19606™ and four carbapenem-resistant A. baumannii (Ab) strains were used. The antibacterial activity of Bio-AgNP and meropenem was evaluated through broth microdilution. The effect of the Bio-AgNP association with meropenem was determined by the checkboard method. Also, the time-kill assay and the integrity of the bacterial cell membrane were evaluated. Furthermore, the antibiofilm activity of Bio-AgNP and meropenem alone and in combination was determined. Bio-AgNP has antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration ranging from 0.46 to 1.87 µg ml-1. The combination of Bio-AgNP and meropenem showed a synergistic and additive effect against Ab strains, and Bio-AgNP was able to reduce the MIC of meropenem from 4- to 8-fold. Considering the time-kill of the cell, meropenem and Bio-AgNP when used in combination reduced bacterial load to undetectable levels within 10 min to 24 h after treatment. Protein leakage was observed in all treatments evaluated. When combined, meropenem/Bio-AgNP presents biofilm inhibition for Ab2 isolate and ATCC® 19606™, with 21% and 19%, and disrupts the biofilm from 22% to 50%, respectively. The increase in nonviable cells in the biofilm can be observed after treatment with Bio-AgNP and meropenem in carbapenem-resistant A. baumannii strains. CONCLUSIONS: The combination of Bio-AgNP with meropenem can be a therapeutic option in the treatment of infections caused by carbapenem-resistant A. baumannii.

Multidrug-resistant Acinetobacter spp. from hospital intensive care units in Brazilian Amazon.

Acinetobacter spp. are one of the main pathogens responsible for healthcare-associated infections and are associated with high rates of morbidity and mortality globally, mainly because of their high capacity to present and develop resistance to antimicrobials. To identify species of the Acinetobacter and their resistance profiles from samples collected from hospitalized patients, health professionals and hospital environmental sources in the intensive care units of different public reference hospitals in Porto Velho City, Rondônia, Western Brazilian Amazon. Isolates were identified using microbiological and molecular techniques. The antimicrobial susceptibility profile was determined by disk diffusion. A total of 201 Acinetobacter spp. isolates were identified, of which 47.3% originated from hospital structures, 46.8% from patients and 6% from healthcare professionals. A. baumannii and A. nosocomialis were the most prevalent, with frequency of 58.7% and 31.8%, respectively. Regarding the susceptibility profile, it was observed that 56.3% were classified as multidrug-resistant and 76.2% of the samples belonging to A. baumannii were resistant to carbapenems. In contrast, 96.9% were susceptible to polymyxin B and 91.3% to doxycycline. The data presented here can be used to guide and strengthen the control of multidrug-resistant infections caused by Acinetobacter spp., in addition to improving providing information from a traditionally unassisted region of Brazil.

In vitro evaluation of human intravenous immunoglobulin in combination with antimicrobials and human serum against multidrug-resistant isolates of Acinetobacter baumannii.

The high incidence of multidrug-resistant (MDR) Acinetobacter baumannii has been a challenge for health worldwide, due to the reduction of therapeutic options, making the use of antimicrobial combinations necessary for the treatment, such as meropenem, amikacin, and colistin. Antibodies against bacterial species, mainly immunoglobulins G (IgG), are produced for acting as effector mechanisms (neutralization, opsonization, phagocytosis, and complement system activation). Some studies have demonstrated promising results of IgG in combination with antimicrobial preparations against bacterial infections, in which the direct action of IgG has restored the immune system balance. Serious problem caused by the increase of MDR A. baumannii isolates results in a constant search for therapeutic alternatives to defeat these infections. However, this study aims to verify in vitro the phagocytosis rate of the A. baumannii-infected human monocytes, as well as to analyze possible morphological changes induced by intravenous immunoglobulin G (IVIG) with human serum in association with antimicrobials. The phagocytosis rate and bacterial cell binding capacity of IVIG were determined for two A. baumannii isolates submitted to 4 mg/mL of human IVIG alone and in combination with different sub-minimum inhibitory concentrations (sub-MICs) of meropenem, amikacin, and colistin and processed for indirect immunofluorescence. Subsequently, these isolates were resubmitted and coupled with human serum and processed for scanning electron microscopy. There was no statistical difference for phagocytosis rates in the isolates tested. Bacterial isolates showed alterations in cell morphology when exposed to IVIG/human serum alone and in combination with antimicrobials such as alteration in shape, wrinkling, membrane depression, and especially cell rupture with extravasation of cytoplasmic material. The isolates visually differed in the IVIG binding to the bacterial cell, with higher fluorescence intensity, which corresponds to the highest IVIG binding, in the isolate more sensitive to meropenem, amikacin, and colistin. No differences between treatments were observed in the IVIG binding to the bacterial cell. The combined action of IVIG with meropenem, amikacin, and colistin against A. baumannii MDR isolates induced several bacterial cell damages. And when associated with human serum, a massive destruction of cells can be observed. These results may suggest the analysis of the use of IgG preparations for the treatment of A. baumannii MDR infections.

Biofilm formation in drug-resistant Acinetobacter baumannii and Acinetobacter nosocomialis isolates obtained from a university hospital in Pelotas, RS, Brazil.

This study aimed to investigate the antibiotic resistance and biofilm formation of Acinetobacter calcoaceticus-A. baumannii (ACB) complex isolates recovered from a university hospital in Pelotas, RS, Brazil. The species were confirmed using gyrB multiplex and blaOXA-51-like genes PCR. The presence of the bfmRS virulence gene was evaluated by the PCR, and the isolates were classified based on their biofilm-forming ability on polystyrene (PO) and glass surfaces (TM). Out of 50 ACB complex isolates evaluated, 41 were identified as A. baumannii and nine as A. nosocomialis. The bfmRS gene was detected in 97.6% (40/41) of A. baumannii and 33.3% (3/9) of A. nosocomialis species. Forty-nine isolates exhibited a multidrug-resistant (MDR) profile, while one A. nosocomialis isolate presented an extensively drug-resistant (XDR) profile. All isolates were able of forming biofilms on PO surfaces and 98% (49/50) on TM surfaces. A significant correlation was observed between biofilm production on PO and TM surfaces (P < 0.05). However, no correlation was found between biofilms forming and the presence of the bfmRS gene or displaying a certain antibiotic resistance profile. In conclusion, A. baumannii and A. nosocomialis are frequent species causing nosocomial infections in a hospital in Pelotas, RS, Brazil, and both are capable of forming biofilms.

Oral doxycycline to carbapenem-resistant Acinetobacter baumannii infection as a polymyxin-sparing strategy: results from a retrospective cohort.

Acinetobacter baumannii infection presents a high mortality rate and few therapeutic options. This study aimed to evaluate clinical-microbiological characteristics and prognosis factors of patients diagnosed with A. baumanni. infections treated with oral doxycycline. A retrospective cohort of hospitalized patients with confirmed Acinetobacter spp. infection between 2018 and 2020 receives at least 3 days of oral doxycycline. Clinical and microbiological data were evaluated, including the outcome and molecular characterization of A. baumannii. Doxycycline minimal inhibitory concentrations were evaluated by the broth dilution method. One hundred patients were included with a median age of 51 years. The leading site of infection was pulmonary (n = 62), followed by the soft tissues and skin (n = 28). A. baumannii resistant to carbapenem was found on 94%. The gene blaOXA-23 and blaOXA-51 were amplified in all recovered isolates of A. baumannii (n = 44). Doxycycline MIC50 and MIC90 were 1 µg/mL and 2 µg/mL, respectively. Death rate at 14 days and 28 days of follow-up was 9% and 14%, respectively. The prognostic factors related to death at end of follow-up were age > 49 years [85.7% vs. 46%, CI 95% 6.9 (1.4-32.6), P = 0.015] and hemodialysis [28.6% vs. 7%, CI 95% 5.33 (1.2-22.1), P = 0.021]. Patients treated with doxycycline to A. baumannii presented a relatively low death rate, and risk factors related to death were age and hemodialysis. Further and larger studies should compare polymyxin to doxycycline to better understand the differences between these therapeutic options.

Therapeutic Prospection of Animal Venoms-Derived Antimicrobial Peptides against Infections by Multidrug-Resistant Acinetobacter baumannii: A Systematic Review of Pre-Clinical Studies.

Infections caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) have become a public health emergency. Due to the small therapeutic arsenal available to treat these infections, health agencies have highlighted the importance of developing new antimicrobials against MDR-Ab. In this context, antimicrobial peptides (AMPs) stand out, and animal venoms are a rich source of these compounds. Here, we aimed to summarize the current knowledge on the use of animal venom-derived AMPs in the treatment of MDR-Ab infections in vivo. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eight studies included in this review identified the antibacterial activity of eleven different AMPs against MDR-Ab. Most of the studied AMPs originated from arthropod venoms. In addition, all AMPs are positively charged and rich in lysine residues. In vivo assays showed that the use of these compounds reduces MDR-Ab-induced lethality and bacterial load in invasive (bacteremia and pneumonia) and superficial (wounds) infection models. Moreover, animal venom-derived AMPs have pleiotropic effects, such as pro-healing, anti-inflammatory, and antioxidant activities, that help treat infections. Animal venom-derived AMPs are a potential source of prototype molecules for the development of new therapeutic agents against MDR-Ab.

High rates of extensively drug-resistant Acinetobacter baumannii in a Peruvian hospital 2013-2019.

Multidrug-resistant (MDR) Acinetobacter baumannii has become a major concern of hospital care. The objective of the study was to evaluate the evolution of antimicrobial resistance of A. baumannii in a Peruvian hospital from 2013 to 2019. A total of 993 A. baumannii clinical isolates were recovered. Antimicrobial resistance levels were extremely high, except for colistin. Among the remaining antibacterial agents, ampicillin plus sulbactam (AMS) was the most active (71.4% of resistance), with resistance levels to the remaining agents ranging from 75.9% to amikacin to 99.2% to ertapenem. The presence of significant differences was observed in extensively drug-resistant (XDR) A. baumannii according to samples origin. No association was observed between MDR or XDR isolates and seasonality. An impressive rate of XDR A. baumannii isolates was found, including a growing number of only-colistin-susceptible isolates highlighting the urgent need for new therapeutic alternatives.