Antibacterial properties of phenothiazine derivatives against multidrug‐resistant Acinetobacter baumannii strains

The stimulation of the immune response to prevent the progression of an infection may be an adjuvant to antimicrobial treatment. Here, we aimed to evaluate the efficacy of lysophosphatidylcholine (LPC) treatment in combination with colistin in murine experimental models of severe infections by Acinetobacter baumannii. We used the A. baumannii Ab9 strain, susceptible to colistin and most of the antibiotics used in clinical settings, and the A. baumannii Ab186 strain, susceptible to colistin but presenting a multidrug-resistant (MDR) pattern. The therapeutic efficacies of one and two LPC doses (25 mg/kg/d) and colistin (20 mg/kg/8 h), alone or in combination, were assessed against Ab9 and Ab186 in murine peritoneal sepsis and pneumonia models. One and two LPC doses combined with colistin and colistin monotherapy enhanced Ab9 and Ab186 clearance from spleen, lungs and blood and reduced mice mortality compared with those of the non-treated mice group in both experimental models. Moreover, one and two LPC doses reduced the bacterial concentration in tissues and blood in both models and increased mice survival in the peritoneal sepsis model for both strains compared with those of the colistin monotherapy group. LPC used as an adjuvant of colistin treatment may be helpful to reduce the severity and the resolution of the MDR A. baumannii infection.

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Antibacterial Activity of Moroccan Zantaz Honey and the Influence of Its Physicochemical Parameters Using Chemometric Tools

Applied Sciences ◽

10.3390/app11104675 ◽

2021 ◽

Vol 11 (10) ◽

pp. 4675

Author(s):

Youssef Elamine ◽

Hamada Imtara ◽

Maria Graça Miguel ◽

Ofélia Anjos ◽

Letícia M. Estevinho ◽

...

Keyword(s):

Antibacterial Activity ◽

Antibacterial Properties ◽

Principal Component ◽

Physicochemical Characteristics ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Coumaric Acid ◽

Atlas Mountains ◽

Methyl Syringate ◽

Chemometric Tools

The emergence of multidrug-resistant bacteria has prompted the development of alternative therapies, including the use of natural products with antibacterial properties. The antibacterial properties of Zantaz honey produced in the Moroccan Atlas Mountains against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus was evaluated and analyzed using chemometric tools. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) against S. aureus were the lowest (112.5 ± 54.5 mg/mL), revealing that this species was most sensitive to Zantaz honey. P. aeruginosa showed an intermediate sensitivity (MIC= 118.75 ± 51.9 mg/mL), while E. coli was the most resistant to treatment (MIC = 175 ± 61.2 mg/mL). Content of monosaccharides, certain minerals, and phenolic compounds correlated with antibacterial activity (p < 0.05). Principal component analysis of physicochemical characteristics and antibacterial activity indicated that the parameters most associated with antibacterial activity were color, acidity, and content of melanoidins, fructose, epicatechin, methyl syringate, 4-coumaric acid, and 3-coumaric acid.

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Radiation-Inactivated Acinetobacter baumannii Vaccine Candidates

Vaccines ◽

10.3390/vaccines9020096 ◽

2021 ◽

Vol 9 (2) ◽

pp. 96

Author(s):

Stephen J. Dollery ◽

Daniel V. Zurawski ◽

Elena K. Gaidamakova ◽

Vera Y. Matrosova ◽

John K. Tobin ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Treatment Options ◽

Bacterial Pathogen ◽

Multidrug Resistant ◽

Bacterial Cells ◽

Wound Infections ◽

Protein Profiles ◽

Vaccine Candidates ◽

Rich Media ◽

Life Threatening

Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80–100% protection.

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Aloe-emodin-mediated antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii: an in vivo study

Photodiagnosis and Photodynamic Therapy ◽

10.1016/j.pdpdt.2021.102311 ◽

2021 ◽

pp. 102311

Author(s):

Yang Wang ◽

Jiao Li ◽

Songmei Geng ◽

Xiaopeng Wang ◽

Zixin Cui ◽

...

Keyword(s):

Photodynamic Therapy ◽

Acinetobacter Baumannii ◽

Multidrug Resistant ◽

In Vivo Study ◽

Antimicrobial Photodynamic Therapy ◽

Aloe Emodin

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1293. Sulbactam-durlobactam is active against recent, multi-drug resistant Acinetobacter baumannii clinical isolates from the Middle East

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1476 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S662-S662

Author(s):

Alita Miller ◽

Sarah McLeod ◽

Samir Moussa ◽

Meredith Hackel

Keyword(s):

Antibacterial Activity ◽

Middle East ◽

Acinetobacter Baumannii ◽

United Arab Emirates ◽

Blood Stream ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Surveillance Systems ◽

Spectrum Activity

Abstract Background The incidence of infections caused by multidrug-resistant (MDR) Acinetobacter baumannii (Ab) is increasing at an alarming rate in certain regions of the world, including the Middle East. Sulbactam (SUL) has intrinsic antibacterial activity against Ab; however, the prevalence of β-lactamases in Ab has limited its therapeutic utility. Durlobactam (DUR, formerly ETX2514) is a diazabicyclooctenone β-lactamase inhibitor with broad-spectrum activity against Ambler class A, C and D β-lactamases that restores SUL activity in vitro against MDR Ab. SUL-DUR is an antibiotic designed to treat serious infections caused by Acinetobacter, including multidrug-resistant strains, that is currently in Phase 3 clinical development. In global surveillance studies of >3600 isolates from 2012-2017, the MIC90 of SUL-DUR was 2 mg/L. Although surveillance systems to monitor MDR infections in the Middle East are currently being established, quantitative, prevalence-based data are not yet available. Therefore, the potency of SUL-DUR was determined against 190 recent, diverse Ab clinical isolates from this region. Methods 190 Ab isolates were collected between 2016 - 2018 from medical centers located in Israel (N = 47), Jordan (N = 36), Qatar (N = 13), Kuwait (N = 42), Lebanon (N = 8), Saudi Arabia (N = 24) and United Arab Emirates (N = 20). Seventy-five percent and 20.5% of these isolates were from respiratory and blood stream infections, respectively. Susceptibility to SUL-DUR and comparator agents was performed according to CLSI guidelines, and data analysis was performed using CLSI and EUCAST breakpoint criteria where available. Results This collection of isolates was 86% carbapenem-resistant and 90% sulbactam-resistant (based on a breakpoint of 4 mg/L). The addition of SUL-DUR (fixed at 4 mg/L) decreased the sulbactam MIC90 from 64 mg/L to 4 mg/L. Only 3 isolates (1.6%) had SUL-DUR MIC values of > 4 mg/L. This potency was consistent across countries, sources of infection and subsets of resistance phenotypes. Conclusion SUL-DUR demonstrated potent antibacterial activity against recent clinical isolates of Ab from the Middle East, including MDR isolates. These data support the global development of SUL-DUR for the treatment of MDR Ab infections. Disclosures Alita Miller, PhD, Entasis Therapeutics (Employee) Sarah McLeod, PhD, Entasis Therapeutics (Employee) Samir Moussa, PhD, Entasis Therapeutics (Employee)

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The Synergistic Effect of Biosynthesized Silver Nanoparticles and Phage ZCSE2 as a Novel Approach to Combat Multidrug-Resistant Salmonella enterica

Antibiotics ◽

10.3390/antibiotics10060678 ◽

2021 ◽

Vol 10 (6) ◽

pp. 678

Author(s):

Abdallah S. Abdelsattar ◽

Rana Nofal ◽

Salsabil Makky ◽

Anan Safwat ◽

Amera Taha ◽

...

Keyword(s):

Silver Nanoparticles ◽

Color Change ◽

Antibacterial Properties ◽

Multidrug Resistant ◽

Inhibitory Effect ◽

Health Concern ◽

Resistant Bacteria ◽

Mortality And Morbidity ◽

Novel Approach ◽

Transmission Electron

The emergence and evolution of antibiotic-resistant bacteria is considered a public health concern. Salmonella is one of the most common pathogens that cause high mortality and morbidity rates in humans, animals, and poultry annually. In this work, we developed a combination of silver nanoparticles (AgNPs) with bacteriophage (phage) as an antimicrobial agent to control microbial growth. The synthesized AgNPs with propolis were characterized by testing their color change from transparent to deep brown by transmission electron microscopy (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). The phage ZCSE2 was found to be stable when combined with AgNPs. Both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated for AgNPs, phage, and their combination. The results indicated that MIC and MBC values were equal to 23 µg/mL against Salmonella bacteria at a concentration of 107 CFU/mL. The combination of 0.4× MIC from AgNPs and phage with Multiplicity of Infection (MOI) 0.1 showed an inhibitory effect. This combination of AgNPs and phage offers a prospect of nanoparticles with significantly enhanced antibacterial properties and therapeutic performance.

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