Drug-resistant Acinetobacter Baumannii Research Articles

Synergistic effects of bacteriophage cocktail and antibiotics combinations against extensively drug-resistant Acinetobacter baumannii

BackgroundThe extensively drug-resistant (XDR) strains of Acinetobacter baumannii have become a major cause of nosocomial infections, increasing morbidity and mortality worldwide. Many different treatments, including phage therapy, are attractive ways to overcome the challenges of antibiotic resistance.MethodsThis study investigates the biofilm formation ability of 30 XDR A. baumannii isolates and the efficacy of a cocktail of four tempetate bacteriophages (SA1, Eve, Ftm, and Gln) and different antibiotics (ampicillin/sulbactam, meropenem, and colistin) in inhibiting and degrading the biofilms of these strains.ResultsThe majority (83.3%) of the strains exhibited strong biofilm formation. The bacteriophage cocktail showed varying degrees of effectiveness against A. baumannii biofilms, with higher concentrations generally leading to more significant inhibition and degradation rates. The antibiotics-bacteriophage cocktail combinations also enhanced the inhibition and degradation of biofilms.ConclusionThe findings suggested that the bacteriophage cocktail is an effective tool in combating A. baumannii biofilms, with its efficacy depending on the concentration. Combining antibiotics with the bacteriophage cocktail improved the inhibition and removal of biofilms, indicating a promising strategy for managing A. baumannii infections. These results contribute to our understanding of biofilm dynamics and the potential of bacteriophage cocktails as a novel therapeutic approach to combat antibiotic-resistant bacteria.

Nosocomial carbapenem-drug resistant Acinetobacter baumannii, related factors and clinical outcomes in Northeast Iran

Background and objectivesNosocomial infections, including drug-resistant Acinetobacter baumannii infections, continue to impact the health of hospitalized patients. This study sought to determine the prevalence of these infections and assess the associated risk factors and clinical outcomes in Gorgan, Iran.MethodsA retrospective cross-sectional study was conducted on 143 infected patients with Acinetobacter baumannii in two educational hospitals in Gorgan city, Iran between 2016 and 2018. Patient information including age, gender, reason and duration of hospitalization, background of diseases, type of sample culture, symptoms, laboratory findings, prescribed antibiotics, and antibiogram were collected and analyzed. The Logistic regression and survival statistical methods were used by software of SPSS 26.ResultsA total of 37 patients (25.87%) died during hospitalization. The less than one year and 45–65 years age groups demonstrated more deaths (29.7%; p-value < 0.001). Being single (not being married) was found to be a risk factor in increasing the chance of death among patients (OR = 2.154, 95% CI: 1.02–4.53; p = 0.048). Hospitalization in intensive care units (ICUs) was a risk factor for the death of patients (OR = 4.655, 95% CI: 7.6–83.2). The resistance to carbapenems was reported to be an important risk factor for the death of patients.ConclusionsAcinetobacter baumannii infections, particularly those resistant to carbapenems, are a significant risk for patients in ICUs and can lead to higher mortality rates.

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.

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.

Risk factors and predictive model for nosocomial infections by extensively drug-resistant Acinetobacter baumannii.

Extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a significant pathogen in hospital environments, particularly in intensive care units (ICUs). XDRAB's resistance to conventional antimicrobial treatments and ability to survive on various surfaces pose a substantial threat to patient health, often resulting in severe infections such as ventilator-associated pneumonia (VAP) and bloodstream infections (BSI). We retrospectively analyzed clinical data from 559 patients with XDRAB infections admitted to Jinhua Central Hospital between January 2021 and December 2023. Patients were randomly divided into a training set (391 cases) and a testing set (168 cases). Variables were selected using Lasso regression and logistic regression analysis, and a predictive model was constructed and validated internally and externally. Model performance and clinical utility were evaluated using the Hosmer-Lemeshow test, C-index, ROC curve, decision curve analysis (DCA), and clinical impact curve (CIC). Lasso regression analysis was used to screen 35 variables, selecting features through 10-fold cross-validation. We chose lambda.1se=0.03450 (log(lambda.1se)=-3.367), including 10 non-zero coefficient features. These features were then included in a multivariate logistic regression analysis, identifying 8 independent risk factors for XDRAB infection: ICU stay of 1-7 days (OR=3.970, 95%CI=1.586-9.937), ICU stay >7 days (OR=12.316, 95%CI=5.661-26.793), hypoproteinemia (OR=3.249, 95%CI=1.679-6.291), glucocorticoid use (OR=2.371, 95%CI=1.231-4.564), urinary catheterization (OR=2.148, 95%CI=1.120-4.120), mechanical ventilation (OR=2.737, 95%CI=1.367-5.482), diabetes mellitus (OR=2.435, 95%CI=1.050-5.646), carbapenem use (OR=6.649, 95%CI=2.321-19.048), and β-lactamase inhibitor use (OR=4.146, 95%CI=2.145-8.014). These 8 factors were used to construct a predictive model visualized through a nomogram. The model validation showed a C-index of 0.932 for the training set and 0.929 for the testing set, with a Hosmer-Lemeshow test p-value of 0.47, indicating good calibration. Furthermore, the DCA curve demonstrated good clinical decision-making performance, and the CIC curve confirmed the model's reliable clinical impact. Regression analysis identified ICU stay duration, hypoproteinemia, glucocorticoid use, urinary catheterization, mechanical ventilation, diabetes mellitus, carbapenem use, and β-lactamase inhibitor use as independent risk factors for XDRAB infection. The corresponding predictive model demonstrated high accuracy and stability.

Screening of the Pandemic Response Box library identified promising compound candidate drug combinations against extensively drug-resistant Acinetobacter baumannii

Infections caused by antimicrobial-resistant Acinetobacter baumannii pose a significant threat to human health, particularly in the context of hospital-acquired infections. As existing antibiotics lose efficacy against Acinetobacter isolates, there is an urgent need for the development of novel antimicrobial agents. In this study, we assessed 400 structurally diverse compounds from the Medicines for Malaria Pandemic Response Box for their activity against two clinical isolates of A. baumannii: A. baumannii 5075, known for its extensive drug resistance, and A. baumannii QS17-1084, obtained from an infected wound in a Thai patient. Among the compounds tested, seven from the Pathogen box exhibited inhibitory effects on the in vitro growth of A. baumannii isolates, with IC50s ≤ 48 µM for A. baumannii QS17-1084 and IC50s ≤ 17 µM for A. baumannii 5075. Notably, two of these compounds, MUT056399 and MMV1580854, shared chemical scaffolds resembling triclosan. Further investigations involving drug combinations identified five synergistic drug combinations, suggesting potential avenues for therapeutic development. The combination of MUT056399 and brilacidin against A. baumannii QS17-1084 and that of MUT056399 and eravacycline against A. baumannii 5075 showed bactericidal activity. These combinations significantly inhibited biofilm formation produced by both A. baumannii strains. Our findings highlight the drug combinations as promising candidates for further evaluation in murine wound infection models against multidrug-resistant A. baumannii. These compounds hold potential for addressing the critical need for effective antibiotics in the face of rising antimicrobial resistance.

The effect of silver nanoparticles on the antimicrobial activity of cloned nisin against extensively drug-resistant Acinetobacter baumannii”

BackgroundAntibiotic resistance is a global threat to human health that leads to disasters. Acinetobacter baumannii cannot be controlled by the existing antibiotics, and it became challenging. Therefore, novel antibacterial agents are required to combat such threats. The aim of this project is to find a novel antimicrobial agent to treat this multi-drug resistant bacterium. MethodsThe NisA gene was isolated from Lactococcus lactis spp. lactis and cloned into the pET-3a plasmid using Gibson cloning assembly. Purified Nisin from cloning was conjugated with silver nanoparticles. Finally, an assessment of antibacterial activity for each of the purified Nisin, Silver nanoparticles, and Nisin-Silver nanoparticles conjugate against the extensively drug-resistant A. baumannii was performed. ResultsNisin was successfully purified from cloned bacteria, and the concentration was 416 µg/ml. The conjugation of nisin and silver nanoparticles was analyzed by electron microscopy. The minimum inhibitory concentration of Nisin and silver nanoparticles against A. baumannii were 104 µg/ml and 125 µg/ml, respectively. While Nisin-silver nanoparticle conjugates showed potent antimicrobial activity with MIC 125–52 µg/ml in which silver nanoparticles increased the antimicrobial activity of nisin beyond its optimum concentration (104 µg/ml). ‎ ConclusionThe development of new antibacterial agents is necessary to control extensively drug-resistant bacteria. Nisin-silver conjugates showed more potent antimicrobial activity than when applied separately and gave hope to combat the multi-drug resistant A. baumannii.

A retrospective study of the efficacy of sulbactam in the treatment of patients with extensively drug-resistant Acinetobacter baumannii infections.

Sulbactam (SBT) is one of the most significant treatments for patients with extensively drug-resistant Acinetobacter baumannii (XDR-AB). However, the efficacy and safety of SBT and its high dose regimen has not been well documented. This retrospective study aimed to assess the efficacy and safety of SBT-based treatment, particularly at high-dose (≥ 6g/day), for XDR-AB infection. A total of 52 XDR-AB infected patients treated with intravenous SBT at Peking Union Medical College Hospital were included. The primary outcome was 28-day all-cause mortality, while the secondary outcome was 14-day clinical response and the time of response. The formulation of SBT in our study is 0.5g per vial. Among the patients, the 28-day all-cause mortality rate was 36.5% (19/52), and the favorable 14-day clinical response rate was 59.6% (31/52). The 28-day mortality was independently associated coinfection with gram-positive bacteria (GPB) and a shorter duration of therapy. Patients with intracranial infection might have a longer survival time. A favorable 14-day clinical response was associated with the dose of SBT, and a longer treatment duration. However, the higher creatinine clearance (CrCl) associated with a worse clincal response. In addition, a higher SBT dosage was significantly correlated with a shorter time to clinical response. No adverse effects related were reported. The single-agent formulation of SBT emerges as a promising alternative for the treatment of XDR-AB infection, such as intracranial infection, particularly at high doses (≥ 6g/day). Besides, longer duration of treatment correlates with higher survival rate and better favorable clinical response. Higher CrCl negatively correlates with favorable clinical response.

Combinations of Antibiotics Effective against Extensively- and Pandrug-Resistant Acinetobacter baumannii Patient Isolates.

Infections due to drug-resistant Acinetobacter baumannii strains are increasing and cause significant morbidity and mortality, especially in hospitalized and critically ill patients. A. baumannii rapidly develops resistance to numerous antibiotics, and antibiotics traditionally used against this deadly pathogen have been failing in recent years, highlighting the need to identify new treatment strategies. Treatment options that have shown promise include revisiting common antibiotics not typically used against A. baumannii, evaluating new antibiotics recently introduced to market, and identifying combinations of antibiotics that display synergistic interactions. In this study, we characterized the antibiotic susceptibility profiles of extensively (XDR) and pandrug-resistant (PDR) A. baumannii patient isolates. We examined the potency of 22 standard-of-care antibiotics and the newer antibiotics eravacycline, omadacycline, and plazomicin against these strains. Furthermore, we examined combinations of these antibiotics against our collection to identify synergistic effects. We found that this collection is highly resistant to most or all standard-of-care antibiotics, except for minocycline and rifampin. We show that eravacycline and omadacycline are effective against these strains based on minimum inhibitory concentrations. We also identified two highly effective combinations, cefepime and amikacin and cefepime and ampicillin-sulbactam, which exhibited high rates of synergy against this collection. This information is valuable in our battle against highly drug resistant and virtually untreatable A. baumannii infections.

The Molecular Typing of Extensively Drug Resistant Acinetobacter baumannii Clinical Isolates Using Arbitrarily Primed PCR (AP-PCR)

The Molecular Typing of Extensively Drug Resistant Acinetobacter baumannii Clinical Isolates Using Arbitrarily Primed PCR (AP-PCR)

Correction: Compassionate use of cefiderocol in a complex case of extensively drug-resistant Acinetobacter baumannii fracture-related infection: a comprehensive approach and multidisciplinary management

Correction: Compassionate use of cefiderocol in a complex case of extensively drug-resistant Acinetobacter baumannii fracture-related infection: a comprehensive approach and multidisciplinary management

Phage therapy combats pan drug-resistant Acinetobacter baumannii infection safely and efficiently

Phage therapy offers a promising approach to combat the growing threat of antimicrobial resistance. Yet, key questions remain regarding dosage, administration routes, combination therapy, and the causes of therapeutic failure. In this study, we focused on a novel lytic phage, ФAb4B, which specifically targeted the Acinetobacter baumannii strains with KL160 capsular polysaccharide, including the pan-drug resistant A. baumannii YQ4. ФAb4B exhibited the ability to effectively inhibit biofilm formation and eradicate mature biofilms independently of dosage. Additionally, it demonstrated a wide spectrum of antibiotic-phage synergy and did not show any cytotoxic or haemolytic effects. Continuous phage injections, both intraperitoneally and intravenously over 7 d, showed no acute toxicity in vivo. Importantly, phage therapy significantly improved neutrophil counts, outperforming ciprofloxacin. However, excessive phage injections suppressed neutrophil levels. The combinatorial treatment of phage-ciprofloxacin rescued 91% of the mice, a superior outcome compared to phage alone (67%). The efficacy of the combinatorial treatment was independent of phage dosage. Notably, prophylactic administration of the combinatorial regimen provided no protection, but even when combined with a delayed therapeutic regimen, it saved all the mice. Bacterial resistance to the phage was not a contributing factor to treatment failure. Our preclinical study systematically describes the lytic phage's effectiveness in both in vitro and in vivo settings, filling in crucial details about phage treatment against bacteriemia caused by A. baumannii, which will provide a robust foundation for the future of phage therapy.

Compassionate use of cefiderocol in a complex case of extensively drug-resistant Acinetobacter baumannii fracture-related infection: a comprehensive approach and multidisciplinary management.

Fracture-related infections (FRI) pose a difficult management problem, as they require numerous surgical interventions and extended antibiotic treatments, especially when a multidrug-resistant organism is involved, with a paucity of available literature that provides guidance. A 42year-old male presents an open diaphyseal tibia and fibula fracture, complicated by soft tissue necrosis and infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-Ab). Initially treated with a damage control external fixator, the patient underwent multiple surgical procedures, including radical debridement, negative pressure wound therapy, external fixator revisions and reconstructive surgery using a latissimus dorsi free flap. The emergence of colistin resistance in the Acinetobacter baumannii strain led to the compassionate use of cefiderocol, finally achieving clinical cure. This case report is one of the firsts that highlights the potential efficacy of cefiderocol in treating challenging bone and joint infections sustained by XDR-Ab. The successful outcome also emphasizes the importance of a comprehensive, multidisciplinary approach in achieving favorable results in complex FRI.

Resistance to bacteriophage incurs a cost to virulence in drug-resistant Acinetobacter baumannii.

Introduction . Acinetobacter baumannii is a critical priority pathogen for novel antimicrobials (World Health Organization) because of the rise in nosocomial infections and its ability to evolve resistance to last resort antibiotics. A. baumannii is thus a priority target for phage therapeutics. Two strains of a novel, virulent bacteriophage (LemonAid and Tonic) able to infect carbapenem-resistant A. baumannii (strain NCTC 13420), were isolated from environmental water samples collected through a citizen science programme.Gap statement. Phage-host coevolution can lead to emergence of host resistance, with a concomitant reduction in the virulence of host bacteria; a potential benefit to phage therapy applications.Methodology. In vitro and in vivo assays, genomics and microscopy techniques were used to characterize the phages; determine mechanisms and impact of phage resistance on host virulence, and the efficacy of the phages against A. baumannii.Results. A. baumannii developed resistance to both viruses, LemonAid and Tonic. Resistance came at a cost to virulence, with the resistant variants causing significantly reduced mortality in a Galleria mellonella larval in vivo model. A replicated 8 bp insertion increased in frequency (~40 % higher frequency than in the wild-type) within phage-resistant A. baumannii mutants, putatively resulting in early truncation of a protein of unknown function. Evidence from comparative genomics and an adsorption assay suggests this protein acts as a novel phage receptor site in A. baumannii. We find no evidence linking resistance to changes in capsule structure, a known virulence factor. LemonAid efficiently suppressed growth of A. baumanni in vitro across a wide range of titres. However, in vivo, while survival of A. baumannii infected larvae significantly increased with both remedial and prophylactic treatment with LemonAid (107 p.f.u. ml-1), the effect was weak and not sufficient to save larvae from morbidity and mortality.Conclusion. While LemonAid and Tonic did not prove effective as a treatment in a Galleria larvae model, there is potential to harness their ability to attenuate virulence in drug-resistant A. baumannii.

Outcome of Acinetobacter baumannii Ventilator Associated Pneumonia in Upper Egypt: does the resistance profile play a role?

Abstract Background Ventilator-associated pneumonia (VAP) due to drug resistant Acinetobacter baumannii (A. baumannii) is a challenging nosocomial problem associated with increased morbidity and risk of mortality. Objective This study aimed to investigate plasmid mediated quinolone resistance genes (PMQR) as a mechanism of resistance transmission, risk factors and outcome of A. baumannii VAP. Methods This prospective cohort study included 100 VAP patients between October 2020 and December 2022. Microbiological confirmation of A. baumannii. was done and PMQR genes were exposed by polymerase chain reaction (PCR). Pneumonia severity index (PSI), risk factors for developing drug resistant A. baumannii VAP, and the outcome were studied. Results The proportions of drug sensitive (DS), multidrug (MDR), extensive drug (XDR), and pan drug (PDR) resistant A. baumannii were 14%, 35%, 50%, and 1%, respectively. Majority of PSI classes IV and V showed XDR (66%) and PDR (100%) isolates. Detection of qnrA, qepA and aac(6′)-Ib-cr genes was predominant in PSI classes IV and V. The in-hospital mortality for MDR, XDR, and PDR was 22.7%, 70.5%, and 2.3%, respectively. ICU duration, prior use of carbapenems and use more than 2 antibiotics prior to VAP were risk factors for developing MDR A. baumannii while septic shock, multilobar chest radiography (CXR) infiltration and PSI class were predictors of in-hospital mortality. Conclusions VAP caused by MDR, XDR and PDR isolates of A. baumannii which harbors qnrA, qepA and aac(6’)-Ib-cr PMQR genes showed higher PSI classes and increased in-hospital mortality. The number of PMQR genes in A. baumannii isolates, ICU days, use of more than 2 antibiotics, and use of carbapenem prior to VAP, were independent risk factors for the development of drug resistant A. baumannii VAP.

Antimicrobial efficacy of eravacycline against emerging extensively drug-resistant (XDR) Acinetobacter baumannii isolates

PurposeDrug-resistant Acinetobacter baumannii is an emerging threat. This study has been conducted to observe the efficacy of eravacycline along with the RND-efflux pump system. MethodsA cross-sectional study was done collecting 48 clinical isolates of Acinetobacter baumannii. MICs of 15 antibiotics were detected along with BMD of tigecycline and eravacycline. PCR products of drug-resistant regulatory genes were sequenced and analyzed. ResultsOf the total 48 Isolates, 35 (72.91%) were XDR and 13 (27.08%) were MDR. Out of all, 60.41% of isolates were found to be susceptible to eravacycline by BMD according to both FDA and EUCAST guidelines. A 2-fold decline of MIC50/90 was observed with the use of eravacycline compared to tigecycline. RND-efflux genes like AdeC in 30 (62.5%) isolates and Regulatory gene AdeS in 29 (60.41%) isolates were detected, explaining the existing resistance mechanism. ConclusionsXDR Acinetobacter poses an escalating threat due to its resistance to multiple antibiotics, raising serious concerns in healthcare settings. Eravacycline is an encouraging new drug for empirical use in severe infection caused due to the same. Molecular investigation and strict antimicrobial stewardship should be followed to control the emergence, and a better understanding of mechanisms of resistance to prevent the spread of drug-resistant isolates.

Isolation and Identification of Effective Probiotics on Drug-Resistant Acinetobacter baumannii Strains and Their Biofilms.

This study aimed to identify, assess, and isolate strong lactobacilli demonstrating broad antibacterial and anti-biofilm activity against drug-resistant strains of Acinetobacter baumannii. Additionally, the mechanism of inhibition of these organisms was to be determined. Over a 6-month period (from December 2021 to June 2022), 53 clinical A. baumannii strains were collected from clinical samples. Twenty probiotic strains were isolated from local dairy products. Antibacterial activity of Lactobacillus strains' cell-free supernatant (CFS) was identified using the agar well diffusion method and the microbroth dilution test. Anti-biofilm effect was performed by the microtiter plate assay. The MTT assay was also used to look into the probiotics' cytotoxic effects on the L929 fibroblast cell line. During the 6-month period, 53 clinical A. baumannii strains were obtained and identified. Out of 20 lactobacillus strains, the CFS of a lactobacillus strain (named L9) showed an inhibitory effect against all A. baumannii strains. Using the broth microdilution method, it was shown that the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of CFS extracts of L9 strains against A. baumannii strains were both ¼ mg/mL. The result of the anti-biofilm showed that the selected probiotic could inhibit biofilm formation. The most common organic acid produced by all Lactobacillus strains, according to the HPLC method, was lactic acid, which was followed by acetic acid. The L929 fibroblast cell line was used in the cytotoxicity assay, which revealed that 100% of the cells in the L929 fibroblast cell line survived treatment with successive doses of CFSs for a full day. The probiotic strain isolated from local yogurt in this study showed potential anti-biofilm and antimicrobial properties against all drug-resistant Acinetobacter isolates. Given the increasing interest in probiotic microorganisms based on their high health benefits, further studies are recommended on the mechanisms of action between probiotics and A. baumannii strains to find new solutions for biological control and treatment of these infections without the use of antibiotics.

Stability study in selected conditions and biofilm-reducing activity of phages active against drug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is currently a serious threat to human health, especially to people with immunodeficiency as well as patients with prolonged hospital stays and those undergoing invasive medical procedures. The ever-increasing percentage of strains characterized by multidrug resistance to widely used antibiotics and their ability to form biofilms make it difficult to fight infections with traditional antibiotic therapy. In view of the above, phage therapy seems to be extremely attractive. Therefore, phages with good storage stability are recommended for therapeutic purposes. In this work, we present the results of studies on the stability of 12 phages specific for A. baumannii under different conditions (including temperature, different pH values, commercially available disinfectants, essential oils, and surfactants) and in the urine of patients with urinary tract infections (UTIs). Based on our long-term stability studies, the most optimal storage method for the A. baumannii phage turned out to be - 70°C. In contrast, 60°C caused a significant decrease in phage activity after 1 h of incubation. The tested phages were the most stable at a pH from 7.0 to 9.0, with the most inactivating pH being strongly acidic. Interestingly, ethanol-based disinfectants caused a significant decrease in phage titers even after 30s of incubation. Moreover, copper and silver nanoparticle solutions also caused a decrease in phage titers (which was statistically significant, except for the Acba_3 phage incubated in silver solution), but to a much lesser extent than disinfectants. However, bacteriophages incubated for 24h in essential oils (cinnamon and eucalyptus) can be considered stable.

Anti-Acinetobacter Baumannii single-chain variable fragments provide therapeutic efficacy in an immunocompromised mouse pneumonia model

BackgroundThe emergence of carbapenem-resistant and extensively drug-resistant (XDR) Acinetobacter baumannii as well as inadequate effective antibiotics calls for an urgent effort to find new antibacterial agents. The therapeutic efficacy of two human scFvs, EB211 and EB279, showing growth inhibitory activity against A. baumannii in vitro, was investigated in immunocompromised mice with A. baumannii pneumonia.ResultsThe data revealed that infected mice treated with EB211, EB279, and a combination of the two scFvs showed better survival, reduced bacterial load in the lungs, and no marked pathological abnormalities in the kidneys, liver, and lungs when compared to the control groups receiving normal saline or an irrelevant scFv.ConclusionsThe results from this study suggest that the scFvs with direct growth inhibitory activity could offer promising results in the treatment of pneumonia caused by XDR A. baumannii.

The physiological role of Acinetobacter baumannii DacC is exerted through influencing cell shape, biofilm formation, the fitness of survival, and manifesting DD-carboxypeptidase and beta-lactamase dual-enzyme activities.

With the growing threat of drug-resistant Acinetobacter baumannii, there is an urgent need to comprehensively understand the physiology of this nosocomial pathogen. As penicillin-binding proteins are attractive targets for antibacterial therapy, we have tried to explore the physiological roles of two putative DD-carboxypeptidases, viz., DacC and DacD, in A. baumannii. Surprisingly, the deletion of dacC resulted in a reduced growth rate, loss of rod-shaped morphology, reduction in biofilm-forming ability, and enhanced susceptibility towards beta-lactams. In contrast, the deletion of dacD had no such effect. Interestingly, ectopic expression of dacC restored the lost phenotypes. The ∆dacCD mutant showed properties similar to the ∆dacC mutant. Conversely, in vitro enzyme kinetics assessments reveal that DacD is a stronger DD-CPase than DacC. Finally, we conclude that DacC might have DD-CPase and beta-lactamase activities, whereas DacD is a strong DD-CPase.