Treatment Of Acinetobacter Baumannii Infections Research Articles

Antibiotic discovery with artificial intelligence for the treatment of Acinetobacter baumannii infections.

Acinetobacter baumannii presents a severe global health threat, with alarming levels of antimicrobial resistance rates resulting in significant morbidity and mortality in the USA, ranging from 26% to 68%, as reported by the Centers for Disease Control and Prevention (CDC). To address this threat, novel strategies beyond traditional antibiotics are imperative. Computational approaches, such as QSAR models leverage molecular structures to predict biological effects, expediting drug discovery. We identified OmpW as a potential therapeutic target in A. baumannii and screened 11,648 natural compounds. We employed QSAR models from a ChEMBL bioactivity data set and conducted structure-based virtual screening against OmpW. Demethoxycurcumin, a lead compound, exhibited promising antibacterial activity against A. baumannii, including multidrug-resistant strains. Additionally, demethoxycurcumin demonstrated anti-virulence properties by reducing A. baumannii interaction with host cells. The findings highlight the potential of artificial intelligence in discovering curcuminoids as effective antimicrobial agents against A. baumannii infections, offering a promising strategy to address antibiotic resistance.

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

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

Current Therapeutic Approaches for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections.

The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial resources, remain dire. Furthermore, A. baumannii superinfections have also occurred during the COVID-19 pandemic. While prevention is important, the antibiotic armamentarium remains the most essential factor for the treatment of these infections. The main problem is the notorious resistance profile (including resistance to carbapenems and colistin) that this bacterium exhibits. While newer beta lactam/beta-lactamase inhibitors have entered clinical practice, with excellent results against various infections due to Enterobacteriaceae, their contribution against A. baumannii infections is almost absent. Hence, we have to resort to at least one of the following, sulbactam, polymyxins E or B, tigecycline or aminoglycosides, against multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Furthermore, the notable addition of cefiderocol in the fight against A. baumannii infections represents a useful addition. We present herein the existing information from the last decade regarding therapeutic advances against MDR/XDR A. baumannii infections.

The Acinetobacter baumannii K70 and K9 capsular polysaccharides consist of related K-units linked by the same Wzy polymerase and cleaved by the same phage depolymerases

ABSTRACT The extensively antibiotic-resistant Acinetobacter baumannii GC1(ST1 IP ) isolate SGH0807 from Singapore carries the KL70 gene cluster. The structure of the K70 capsular polysaccharide (CPS) produced by SGH0807 was determined using sugar analysis and one- and two-dimensional 1 H and 13 C NMR spectroscopy. The K70 CPS consists of branched tetrasaccharide K-units and is closely related to the previously reported K9 CPS. The KL70 and KL9 loci differ in a short segment that encodes the initiating transferase for d -Fuc p NAc in K70 and d -Glc p NAc in K9. The two structures differ only in the identity of the “first” sugar of the K-unit, d -Fuc p NAc in K70 and d -Glc p NAc in K9. This difference alters the identity of one of the sugars involved in the linkage between K-units formed by the Wzy polymerase. However, KL70 and KL9 encode an identical Wzy polymerase, designated as Wzy KL9 , indicating that the differences between d -Fuc p NAc and d -Glc p NAc do not affect its function. Whether the difference in the first sugars was recognized by the depolymerases encoded by three K9-specific bacteriophages, AM24, BS46, and APK09, that hydrolyze the bond in K9 CPS formed by Wzy KL9 was also examined. Purified depolymerases incubated with K70 CPS purified from SGH0807 formed oligosaccharide fragments that were monomers and dimers of the CPS cleaved at the linkage between K-units. As depolymerases encoded by phage determine host specificity by hydrolyzing specific CPS types, these phages could infect and lyse the SGH0807 K70 isolate. A. baumannii carrying KL70 were found in Singapore hospitals between 2006 and 2009. IMPORTANCE Bacteriophage show promise for the treatment of Acinetobacter baumannii infections that resist all therapeutically suitable antibiotics. Many tail-spike depolymerases encoded by phage that are able to degrade A. baumannii capsular polysaccharide (CPS) exhibit specificity for the linkage present between K-units that make up CPS polymers. This linkage is formed by a specific Wzy polymerase, and the ability to predict this linkage using sequence-based methods that identify the Wzy at the K locus could assist with the selection of phage for therapy. However, little is known about the specificity of Wzy polymerase enzymes. Here, we describe a Wzy polymerase that can accommodate two different but similar sugars as one of the residues it links and phage depolymerases that can cleave both types of bond that Wzy forms.

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.

Synergistic combination of carvedilol, amlodipine, amitriptyline, and antibiotics as an alternative treatment approach for the susceptible and multidrug-resistant A. baumannii infections via drug repurposing.

We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of Acinetobacter baumannii infections caused by susceptible and multidrug-resistant strains. A. baumannii is a multidrug-resistant Gram-negative bacteria causing nosocomial infections, especially in intensive care units. It has been identified in the WHO critical pathogen list and this emphasises urgent need for new treatment options. As the development of new therapeutics is expensive and time consuming, finding new uses of existing drugs via drug repositioning has been favoured. Antimicrobial susceptibility tests were conducted on all 13 drugs according to CLSI. Drugs with MIC values below 128 μg/mL and control antibiotics were further subjected to synergetic effect and bacterial time-kill analysis. Carvedilol-gentamicin (FICI 0.2813) and carvedilol-amlodipine (FICI 0.5625) were determined to have synergetic and additive effect, respectively, on the susceptible A. baumannii strain, and amlodipine-tetracycline (FICI 0.75) and amitriptyline-tetracycline (FICI 0.75) to have additive effect on the multidrug-resistant A. baumannii strain. Most remarkably, both amlodipine and amitriptyline reduced the MIC of multidrug-resistant, including some carbapenems, A. baumannii reference antibiotic tetracycline from 2 to 0.5 μg/mL, for 4-folds. All these results were further supported by bacterial time-kill assay and all combinations showed bactericidal activity, at certain hours, at 4XMIC. Combinations proposed in this study may provide treatment options for both susceptible and multidrug-resistant A. baumannii infections but requires further pharmacokinetics and pharmacodynamics analyses and in vivo re-evaluations using appropriate models.

A fresh pH-responsive imipenem-loaded nanocarrier against Acinetobacter baumannii with a synergetic effect.

In recent years, the treatment of Acinetobacter baumannii infections has become a pressing clinical challenge due to its increasing incidence and its serious pathogenic risk. The research and development of new antibacterial agents for A. baumannii have attracted the attention of the scientific community. Therefore, we have constructed a new pH-responsive antibacterial nano-delivery system (Imi@ZIF-8) for the antibacterial treatment of A. baumannii. Due to its pH-sensitive characteristics, the nano-delivery system offers an improved release of the loaded imipenem antibiotic at the acidic infection site. Based on the high loading capacity and positive charge of the modified ZIF-8 nanoparticles, they are excellent carriers and are suitable for imipenem loading. The Imi@ZIF-8 nanosystem features synergistic antibacterial effects, combining ZIF-8 and imipenem to eliminate A. baumannii through different antibacterial mechanisms. When the loaded imipenem concentration reaches 20µg/mL, Imi@ZIF-8 is highly effective against A. baumannii in vitro. Imi@ZIF-8 not only inhibits the biofilm formation of A. baumannii but also has a potent killing effect. Furthermore, in mice with celiac disease, the Imi@ZIF-8 nanosystem demonstrates excellent therapeutic efficacy against A. baumannii at imipenem concentrations of 10mg/kg, and it can inhibit inflammatory reaction and local leukocyte infiltration. Due to its biocompatibility and biosafety, this nano-delivery system is a promising therapeutic strategy in the clinical treatment of A. baumannii infections, providing a new direction for the treatment of antibacterial infections.

Metabolomic profiling of polymyxin-B in combination with meropenem and sulbactam against multi-drug resistant Acinetobacter baumannii.

Empirical therapies using polymyxins combined with other antibiotics are recommended in the treatment of Acinetobacter baumannii infections. In the present study, the synergistic activities of polymyxin-B, meropenem, and sulbactam as combination therapy were investigated using metabolomic analysis. The metabolome of A. baumannii was investigated after treatment with polymyxin-B alone (2 mg/l), meropenem (2 mg/l) alone, combination of polymyxin-B/meropenem at their clinical breakpoints, and triple-antibiotic combination of polymyxin-B/meropenem and 4 mg/l sulbactam. The triple-antibiotic combination significantly changed the metabolite levels involved in cell outer membrane and cell wall biosynthesis, including fatty acid, glycerophospholipid, lipopolysaccharide, peptidoglycan, and nucleotide within 15 min of administration. In contrast, significant changes in metabolome were observed after 1 h in sample treated with either meropenem or polymyxin-B alone. After 1 h of administration, the double and triple combination therapies significantly disrupted nucleotide and amino acid biosynthesis pathways as well as the central carbon metabolism, including pentose phosphate and glycolysis/gluconeogenesis pathways, and tricarboxylic acid cycle. The addition of sulbactam to polymyxin-B and meropenem combination appeared to be an early disruptor of A. baumannii metabolome, which paves the way for further antibiotic penetration into bacteria cells. Combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can effectively confer susceptibility to A. baumannii harboring OXA-23 and other drug resistant genes. Metabolomic profiling reveals underlying mechanisms of synergistic effects of polymyxin-B combined with meropenem and sulbactam against multi-drug resistant A. baumannii.

Identification and characterization of potential druggable targets among Essential Hypothetical Proteins of A. baumannii

Acinetobacter baumannii, a gram negative bacteria, has emerged as a critical pathogen responsible for nosocomial and other infections. A. baumannii exhibits resistance to a variety of antibiotic classes, emphasizing that new therapeutic targets are urgently needed. In A. baumannii, ATCC 179778, 458 genes have been identified as essential genes, indispensable for growth and survival of the pathogen. The functions of 47 proteins encoded by A.baumannii essential genes were found to be hypothetical and thus referred as essential hypothetical proteins (EHPs). The present study aims to carry out functional characterization of EHPs using bioinformatics tools/databases. Evaluation of physicochemical parameters, homology search against known proteins, domain analysis, subcellular localization analysis, 3D structure prediction and virulence prediction assisted us to characterize EHPs. They belong to different functional classes like enzymes, binding proteins, helicases, transporters, miscellaneous proteins and virulence factors. Around 47% of EHPs were enzymes. A group of EHPs (17.6%) were predicted as virulence factors. Proteins present in the pathogen but absent in the host were identified using host non-homology analysis. Further druggability analysis examined the druggable property of the proteins. Of 34, 27 essential pathogen-specific proteins which could serve as potential novel drug and vaccine targets. Druggability analysis was performed to examined the druggable property of the proteins. One target was found to be druggable and others were novel targets. The study's findings might assist in the development of new drugs for the treatment of Acinetobacter baumannii infections.

Colistin Monotherapy versus Colistin plus Meropenem Combination Therapy for the Treatment of Multidrug-Resistant Acinetobacter baumannii Infection: A Meta-Analysis

(1) Introduction: Colistin combination therapy with other antibiotics is a way to enhance colistin activity. The purpose of this meta-analysis was to compare the efficacy and safety of treatment with colistin monotherapy versus colistin plus meropenem combination therapy in patients with drug-resistant Acinetobacter baumannii infection. (2) Methods: All studies were included if they reported one or more of the following outcomes: clinical improvement, complete microbiological response, 14-day mortality, hospital mortality, or nephrotoxicity. (3) Results: Three randomized controlled trials and seven retrospective studies were included in the meta-analysis. Colistin monotherapy has similar rates of clinical improvement, 14-day mortality, hospital mortality, and nephrotoxicity as colistin plus meropenem combination therapy. Regarding complete microbiological response, the colistin plus meropenem combination was better than colistin monotherapy. (4) Discussion: Previous meta-analyses demonstrated heterogeneity in study quality and a lack of evidence supporting the use of colistin-based combination therapy. Our meta-analysis clearly showed that colistin combined with meropenem was not superior to colistin monotherapy for the treatment of Acinetobacter baumannii infection. (5) Conclusions: The efficacy and safety of treatment with colistin monotherapy and that of colistin plus meropenem combination therapy in patients with drug-resistant Acinetobacter baumannii infection were comparable. The majority of the evidence was obtained from nonrandomized studies, and high-quality randomized controlled trials are needed to confirm the role of colistin plus meropenem combination therapy in the treatment of multidrug-resistant Acinetobacter baumannii infection.

6-Bromo-2-naphthol from Silene armeria extract sensitizes Acinetobacter baumannii strains to polymyxin

The overuse of antibiotics has led to the emergence of multidrug-resistant bacteria, which are resistant to various antibiotics. Combination therapies using natural compounds with antibiotics have been found to have synergistic effects against several pathogens. Synergistic natural compounds can potentiate the effects of polymyxins for the treatment of Acinetobacter baumannii infection. Out of 120 types of plant extracts, only Silene armeria extract (SAE) showed a synergistic effect with polymyxin B (PMB) in our fractional inhibitory concentration and time-kill analyses. The survival rate of G. mellonella infected with A. baumannii ATCC 17978 increased following the synergistic treatment. Interestingly, the addition of osmolytes, such as trehalose, canceled the synergistic effect of SAE with PMB; however, the underlying mechanism remains unclear. Quadrupole time-of-flight liquid chromatography-mass spectrometry revealed 6-bromo-2-naphthol (6B2N) to be a major active compound that exhibited synergistic effects with PMB. Pretreatment with 6B2N made A. baumannii cells more susceptible to PMB exposure in a time- and concentration-dependent manner, indicating that 6B2N exhibits consequential synergistic action with PMB. Moreover, the exposure of 6B2N-treated cells to PMB led to higher membrane leakage and permeability. The present findings provide a promising approach for utilizing plant extracts as adjuvants to reduce the toxicity of PMB in A. baumannii infection.

Treatment of Acinetobacter baumannii infection after total hip arthroplasty with debridement, irrigation, antibiotics and implant retention

Joint Diseases and Related Surgery (JDRS), the official journal of the Turkish Joint Diseases Foundation, is an international, peer-reviewed, immediate open access journal. All published articles in JDRS has been free for everyone, without embargo, since 1990.

In Vivo Evaluation of ECP Peptide Analogues for the Treatment of Acinetobacter baumannii Infection.

Antimicrobial peptides (AMPs) are alternative therapeutics to traditional antibiotics against bacterial resistance. Our previous work identified an antimicrobial region at the N-terminus of the eosinophil cationic protein (ECP). Following structure-based analysis, a 30mer peptide (ECPep-L) was designed that combines antimicrobial action against Gram-negative species with lipopolysaccharides (LPS) binding and endotoxin-neutralization activities. Next, analogues that contain non-natural amino acids were designed to increase serum stability. Here, two analogues were selected for in vivo assays: the all-D version (ECPep-D) and the Arg to Orn version that incorporates a D-amino acid at position 2 (ECPep-2D-Orn). The peptide analogues retained high LPS-binding and anti-endotoxin activities. The peptides efficacy was tested in a murine acute infection model of Acinetobacter baumannii. Results highlighted a survival rate above 70% following a 3-day supervision with a single administration of ECPep-D. Moreover, in both ECPep-D and ECPep-2D-Orn peptide-treated groups, clinical symptoms improved significantly and the tissue infection was reduced to equivalent levels to mice treated with colistin, used as a last resort in the clinics. Moreover, treatment drastically reduced serum levels of TNF-α inflammation marker within the first 8 h. The present results support ECP-derived peptides as alternative candidates for the treatment of acute infections caused by Gram-negative bacteria.

Prevalence of \u03b2-lactamase-encoding genes and molecular typing of Acinetobacter baumannii isolates carrying carbapenemase OXA-24 in children

Backgroundβ-Lactam antibiotics have been broadly used for the treatment of Acinetobacter baumannii infections, resulting in development of β-lactam inactivating β-lactamases. Here, we described antibiotic resistance rate, prevalence of β-lactamase-encoding genes, and clonal relationships of A. baumannii strains isolated from children referred to Children’s Medical Center in Tehran, Iran, during 2019–2020.MethodsA total of 60 non-replicate A. baumannii isolates were recovered from clinical specimens of pediatric patients. Antibiotic susceptibility testing was done by the disc diffusion method. Colistin susceptibility of isolates was performed by the broth microdilution method. β-lactamase-encoding genes were characterized by PCR. The presence of ISAba1 element upstream of the several oxacillinase genes was also checked. Genetic relatedness of isolates was determined by using random amplification of polymorphic DNA (RAPD) typing.ResultsThe antimicrobial susceptibility tests showed that 83.3% of A. baumannii isolates were MDR, and 40% XDR. Both MDR and XDR A. baumannii isolates were susceptible to colistin. The frequency of blaOXA-51-like, blaOXA-23-like, blaTEM, blaOXA-24-like, blaPER, blaSHV, blaCTX-M, blaOXA-58-like, and blaIMP was 100, 93.33, 60, 36.67, 28.33, 8.33, 5, 3.33, and 1.67%, respectively. Coexistence of ISAba1/blaOXA-23-like and ISAba1/blaOXA-51-like was observed in 65% and 85% of isolates, respectively. RAPD analysis revealed 4 common types and 2 single types of A. baumannii isolates.ConclusionsThe multiple clones harboring blaOXA-23-like, ISAba1-blaOXA-51-like, and ISAba1-blaOXA-23-like were responsible for the spread of A. baumannii isolates in our clinical wards. Dissemination of the well-established clones is worrisome and would become therapeutic challenges due to the possible transferring genetic elements associated with resistance.

Contemporary Perspective on the Treatment of Acinetobacter baumannii Infections: Insights from the Society of Infectious Diseases Pharmacists.

The purpose of this narrative review is to bring together the most recent epidemiologic, preclinical, and clinical findings to offer our perspective on best practices for managing patients with A. baumannii infections with an emphasis on carbapenem-resistant A. baumannii (CRAB). To date, the preferred treatment for CRAB infections has not been defined. Traditional agents with retained in vitro activity (aminoglycosides, polymyxins, and tetracyclines) are limited by suboptimal pharmacokinetic characteristics, emergence of resistance, and/or toxicity. Recently developed and US Food and Drug Administration (FDA)-approved β-lactam/β-lactamase inhibitor agents do not provide enhanced activity against CRAB. On balance, cefiderocol and eravacycline demonstrate potent in vitro activity and are well tolerated, but clinical data for patients with CRAB infections do not yet support widespread use. Given that CRAB has the capacity to infect vulnerable patients and preferred regimens have not been identified, we advocate for combination therapy. Our preferred regimen for critically ill patients infected, or considered to be at high risk for CRAB, includes meropenem, polymyxin B, and ampicillin/sulbactam. Importantly, site of infection, severity of illness, and local epidemiology are essential factors to be considered in selecting combination therapies. Molecular mechanisms of resistance may unveil preferred combinations at individual centers; however, such data are often unavailable to treating clinicians and have not been linked to improved clinical outcomes. Combination strategies may also pose an increased risk for antibiotic toxicity and Clostridioides difficile infection, and should therefore be balanced by understanding patient goals of care and underlying health conditions. Promising therapies that are in clinical development and/or under investigation include durlobactam–sulbactam, cefiderocol combination regimens, and bacteriophage therapy, which may over time eliminate the need for the continued use of polymyxins. Future goals for CRAB management include pathogen-focused treatment paradigms that are based on molecular mechanisms of resistance, local susceptibility rates, and the availability of well-tolerated, effective treatment options.

Efflux Pump Overexpression Profiling in Acinetobacter baumannii and Study of New 1-(1-Naphthylmethyl)-Piperazine Analogs as Potential Efflux Inhibitors.

Overexpression of efflux pumps extruding antibiotics currently used for the treatment of Acinetobacter baumannii infections has been described as an important mechanism causing antibiotic resistance. The first aim of this work was to phenotypically evaluate the overexpression of efflux pumps on a collection of 124 ciprofloxacin-resistant A. baumannii strains. An overexpression of genes encoding one or more efflux pumps was obtained for 19 out of the 34 strains with a positive phenotypic efflux (56%). The most frequent genes overexpressed were those belonging to the RND family, with adeJ being the most prevalent (50%). Interestingly, efflux pump genes coding for MATE and MFS families were also overexpressed quite frequently: abeM (32%) and abaQ (26%). The second aim was to synthesize 1-(1-naphthylmethyl)-piperazine analogs as potential new efflux pump inhibitors and biologically evaluate them against strains with a positive phenotypic efflux. Quinoline and pyridine analogs were found to be more effective than their parent compound, 1-(1-naphthyl methyl)-piperazine. Stereochemistry also played an important part in the inhibitory activity, as quinoline derivative (R)-3a was identified as being the most effective and less cytotoxic. Its inhibitory activity was also correlated with the number of efflux pumps expressed by a strain. The results obtained in this work suggest that quinoline analogs of 1-(1-naphthylmethyl)-piperazine are promising leads in the development of new anti-Acinetobacter baumannii therapeutic alternatives in combination with antibiotics for which an efflux-mediated resistance is suspected.

A Pilot Study of Antibiotic Regimens for Infections Caused by Acinetobacter baumannii in a Secondary Hospital in Thailand.

PurposeThis retrospective pilot study aimed to investigate the antibiotic regimens used to treat Acinetobacter baumannii infections at a secondary hospital in southern Thailand. Additionally, the clinical outcomes and mortality of each regimen are described.Patients and MethodsThe medical charts of all patients admitted to Phang-Nga Hospital, Thailand, between 1 January 2019 and 31 May 2020 due to Acinetobacter baumannii infection were reviewed. Data were collected on the antibiotics that patients received before and after sensitivity testing, along with the clinical cure, mortality rates, and nephrotoxicity.ResultsOf the 32 inpatients recruited in the study, the most prescribed antibiotic regimen for empirical therapy was beta-lactam/beta-lactamase inhibitor monotherapy (22%), and for definitive therapy was meropenem monotherapy (28%). Combination therapy with two, three, or four antibiotics was prescribed less than 50% of cases for both empirical and definitive therapy. Moreover, the results indicated that patients receiving combination therapy had a lower clinical response and higher mortality than those receiving monotherapy. Furthermore, regimens containing colistin did not provide a higher clinical cure compared to those without colistin.ConclusionThe results of this pilot study support the use of monotherapy antibiotic regimens, including ceftazidime and meropenem, for the treatment of Acinetobacter baumannii infections in secondary hospitals. However, as these results are from a single hospital with limited number of patients, the application of the results should be done carefully. More patient data from other hospitals will be collected in the next phase of this study.

A comprehensive and contemporary “snapshot” of β-lactamases in carbapenem resistant Acinetobacter baumannii

Successful treatment of Acinetobacter baumannii infections require early and appropriate antimicrobial therapy. One of the first steps in this process is understanding which β-lactamase (bla) alleles are present and in what combinations. Thus, we performed WGS on 98 carbapenem-resistant A. baumannii (CR Ab). In most isolates, an acquired blaOXA carbapenemase was found in addition to the intrinsic blaOXA allele. The most commonly found allele was blaOXA-23 (n = 78/98). In some isolates, blaOXA-23 was found in addition to other carbapenemase alleles: blaOXA-82 (n = 12/78), blaOXA-72 (n = 2/78) and blaOXA-24/40 (n = 1/78). Surprisingly, 20% of isolates carried carbapenemases not routinely assayed for by rapid molecular diagnostic platforms, i.e., blaOXA-82 and blaOXA-172; all had ISAba1 elements. In 8 CR Ab, blaOXA-82 or blaOXA-172 was the only carbapenemase. Both blaOXA-24/40 and its variant blaOXA-72 were each found in 6/98 isolates. The most prevalent ADC variants were blaADC-30 (21%), blaADC-162 (21%), and blaADC-212 (26%). Complete combinations are reported.

Synthesis of 4,4'-(4-Formyl-1H-pyrazole-1,3-diyl)dibenzoic Acid Derivatives as Narrow Spectrum Antibiotics for the Potential Treatment of Acinetobacter Baumannii Infections.

Acinetobacter baumannii has emerged as one of the most lethal drug-resistant bacteria in recent years. We report the synthesis and antimicrobial studies of 25 new pyrazole-derived hydrazones. Some of these molecules are potent and specific inhibitors of A. baumannii strains with a minimum inhibitory concentration (MIC) value as low as 0.78 µg/mL. These compounds are non-toxic to mammalian cell lines in in vitro studies. Furthermore, one of the potent molecules has been studied for possible in vivo toxicity in the mouse model and found to be non-toxic based on the effect on 14 physiological blood markers of organ injury.

Coexistence of genes encoding aminoglycoside modifying enzymes among clinical Acinetobacter baumannii isolates in Ahvaz, Southwest Iran.

Aminoglycosides are widely recommended for treatment of Acinetobacter baumannii infections in combination with β-lactams or quinolones. This cross-sectional study was aimed to investigate the coexistence of aminoglycoside modifying enzyme (AME) genes among A. baumannii isolates from clinical samples in Ahvaz, Iran. A total of 85 clinical A. baumannii isolates typed by ERIC-PCR were investigated for the presence of AME genes, including ant(3″)-Ia, aac(6')-Ib, aac(3')-Ia, ant(2″)-Ia, and aph(3')-VIa by PCR. The resistance rates to aminoglycoside agents were evaluated by disk diffusion. In this study, 84 out of 85 A. baumannii isolates were resistant to at least one of the aminoglycosides and harbored at least one AME gene. The most common gene encoding AMEs was aph (3')VIa, followed by aac(3')-Ia, ant(3″)-Ia, ant (2″)-Ia, and aac(6')-Ib. The aminoglycoside-resistant genotypes were completely matched to resistant phenotypes to each one of the aminoglycoside agents. There was a clear association between AME gene types and the phenotype of resistance to aminoglycosides with their ERIC-PCR types. Our findings highlight the coexistence of AME genes and clonal dissemination of multiresistant A. baumannii in hospital setting.