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This study investigated the antibacterial and anti-biofilm properties of postbiotics derived from Lactobacillus plantarum and their effect on the expression of antibiotic resistance genes (ermB and blaKPC) in Enterococcus faecalis and Pseudomonas aeruginosa , respectively. Cell-free supernatants (CFSs) were analyzed through gas chromatography–mass spectrometry (GC-MS), which showed that butyric acid (14.31%) was the major compound, other metabolites present in CFSs included lactic acid (5.94%), hdroxyacetone (5,21%), benzoic acid (3.12%), Pyrrolo[1,2-a] pyrazine-1,4-dione (1.91%), 2,3-Butanediol (1.04%), and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (0.73.%). To investigate the effect of postbiotics on bacterial growth and biofilm formation, minimal inhibitory concentration (MIC) and microtiter plate assays were used. MIC results showed that resistant En. faecalis and P. aeruginosa can grow at concentrations of 2.5 and 5 mg/ml, respectively, after exposure to postbiotics. Furthermore, the microtiter plate results showed that postbiotics significantly reduced biofilm formation: 51%, 45%, and 39% in En. faecalis and 46%, 38%, and 27% in P. aeruginosa at different concentrations. Real-time polymerase chain reaction also confirmed the reduction of resistance genes (ermB; P  = 0.007 and blaKPC; P  = 0.02) expression. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that the cell survival rate was 80%. These findings suggest that postbiotics from L. plantarum may be a promising approach for combating bacterial growth, biofilm formation, and antibiotic resistance. [ABSTRACT FROM AUTHOR]

The high frequency of P. aeruginosa was found in pus, urine and section tip in collected clinical samples as they yielded the isolates 32, 16 and 12 in number. Antibiotic susceptibility pattern reveals that cefeprime (n = 44) was the most effective drug against most of the isolated Pseudomonas aeruginosa pathogen followed by meropenem (n = 43), gentamicin (n=42) and amikacin (n=41), whereas moderate to least susceptibility was recorded against levofloxacin (n = 37), piperacillin and ciprofloxacin (n = 36), imepenem (n=34), ceftazidime (n=31), colistin (n=01). In the current study, carried out in Shri Mahant Indiresh Hospital, Dehradun (A tertiary care hospital) indicated the high prevalence of P. aeruginosa among patients of varied age group (from children to elderly people). Most vulnerable age group were from 20yr to 40 yr and 40yr to 60yr. The highest numbers of Pseudomonas aeruginosa were isolated from male patient (69%) in comparison to the female patient i.e., (31%). [ABSTRACT FROM AUTHOR]

Modern functional chemicals that can be employed in biotechnology, pharmaceutics, and food science are a sustainable source to be found in seaweeds. The bioactivity of the majority of these marine compounds has received scant research. Fucoidan is a highly sulfated polysaccharide with a range of bioactivities, including an antipathogenic effect. There is still much to learn about the relationship between fucoidan structure and its function in pathogen infections. By employing microwave and probe sonication to create crude fucoidan, DEAE-cellulose anion-exchange chromatography was used to further purify the substance. Purified fucoidan was structurally characterized using UV–Visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and NMR analysis. The results of the structural analysis demonstrate that sulfates and hydroxyl groups are present in the isolated fucoidan. There are fucose residues, according to the NMR data. The present study investigates the bioactivity of fucoidan, a polysaccharide derived from the brown algae Padina boryana, as a potent weapon against the known nosocomial diseases Proteus vulgaris and Salmonella enterica. Fluorescence microscopy was used to show that fucoidan antibiofilm action is totally effective against Proteus vulgaris and Salmonella enterica biofilm formations as well as planktonic cell growths at dosages over 25 g/mL. Here, using in vitro investigations of the possible inactivation of molecules that are regulated by acyl-homoserine lactone (AHL) in both bacterial species, we explore the antiquarum sensing and antibiofilm capabilities of fucoidan. According to the present study, extracted fucoidan from Padina boryana can be used to generate antibacterial compounds and operate as a quorum-sensing inhibitor to combat side effects and antibiotic resistance. [ABSTRACT FROM AUTHOR]

Multi-drug-resistant (MDR) Acinetobacter baumannii is an opportunistic pathogen associated with hospital-acquired infections. Due to its environmental persistence, virulence, and limited treatment options, this organism causes both increased patient mortality and incurred healthcare costs. Thus, prophylactic vaccination could be ideal for intervention against MDR Acinetobacter infection in susceptible populations. In this study, we employed immunoinformatics to identify peptides containing both putative B- and T-cell epitopes from proteins associated with A. baumannii pathogenesis. A novel Acinetobacter Multi-Epitope Vaccine (AMEV2) was constructed using an A. baumannii thioredoxin A (TrxA) leading protein sequence followed by five identified peptide antigens. Antisera from A. baumannii infected mice demonstrated reactivity to rAMEV2, and subcutaneous immunization of mice with rAMEV2 produced high antibody titer against the construct as well as peptide components. Immunization results in increased frequency of IL-4-secreting splenocytes indicative of a Th2 response. AMEV2-immunized mice were protected against intranasal challenge with a hypervirulent strain of A. baumannii and demonstrated reduced bacterial burden at 48 h. In contrast, all mock vaccinated mice succumbed to infection within 3 days. Results presented here provide insight into the effectiveness of immunoinformatic-based vaccine design and its potential as an effective strategy to combat the rise of MDR pathogens. [ABSTRACT FROM AUTHOR]

Achromobacter xylosoxidans is an emerging nosocomial pathogen which is commonly found in the environment. In hospital settings, especially in ICU, it can be a cause of nosocomial infection. It is commonly found in the humidifiers in ICU settings and it is also commonly associated with the immunocompromised state of patient having comorbidities. The objective of the study was to study the prevalence of Achromobacter xylosoxidans and its antimicrobial sensitivity pattern. The Retrospective analysis was done of the culture reports positive for Achromobacter xylosoxidans by VITEK 2 method and its Antimicrobial sensitivity pattern was analysed from the period of September 2021 to February 2023.The maximum (54.54%) infection was seen in the age group >50 years. The maximum number (66.2%) of Achromobacter xylosoxidans were isolated from Suction tip, followed by blood (8%) and Tracheal Tip (5%). Surgical ICU contributed to the maximum number of infections i.e. 40.2%, followed by Respiratory ICU (22.1%). Maximum sensitivity was seen for Cotrimoxazole and Meropenem (around 80%), followed by Cefoperazone-Sulbactam (74%), Imipenem, Levofloxacin, Ceftazidime (around 65%). The sensitivity was minimal for Ceftriaxone (0%), Aztreonam (1.3%), and Gentamicin (5.2%). The most common risk factors/ comorbidities associated with Achromobacter infections was recent ICU admission (87.01%). The antibiotic sensitivity trends to all the antibiotics used, declined from 2021 to 2022. The antibiotic of choice to our conclusion is Cotrimoxazole, followed by Piperacillin-Tazobactam. Colistin should be kept as a reserve drug for the last resort treatment. The bacteria should not be ignored as it can lead to various opportunistic infections in immunocompromised patients, causing hindrance in the treatment.

Achromobacter xylosoxidans is an emerging nosocomial pathogen which is commonly found in the environment. In hospital settings, especially in ICU, it can be a cause of nosocomial infection. It is commonly found in the humidifiers in ICU settings and it is also commonly associated with the immunocompromised state of patient having comorbidities. The objective of the study was to study the prevalence of Achromobacter xylosoxidans and its antimicrobial sensitivity pattern. The Retrospective analysis was done of the culture reports positive for Achromobacter xylosoxidans by VITEK 2 method and its Antimicrobial sensitivity pattern was analysed from the period of September 2021 to February 2023.The maximum (54.54%) infection was seen in the age group >50 years. The maximum number (66.2%) of Achromobacter xylosoxidans were isolated from Suction tip, followed by blood (8%) and Tracheal Tip (5%). Surgical ICU contributed to the maximum number of infections i.e. 40.2%, followed by Respiratory ICU (22.1%). Maximum sensitivity was seen for Cotrimoxazole and Meropenem (around 80%), followed by Cefoperazone-Sulbactam (74%), Imipenem, Levofloxacin, Ceftazidime (around 65%). The sensitivity was minimal for Ceftriaxone (0%), Aztreonam (1.3%), and Gentamicin (5.2%). The most common risk factors/ comorbidities associated with Achromobacter infections was recent ICU admission (87.01%). The antibiotic sensitivity trends to all the antibiotics used, declined from 2021 to 2022. The antibiotic of choice to our conclusion is Cotrimoxazole, followed by Piperacillin-Tazobactam. Colistin should be kept as a reserve drug for the last resort treatment. The bacteria should not be ignored as it can lead to various opportunistic infections in immunocompromised patients, causing hindrance in the treatment. [ABSTRACT FROM AUTHOR]

There exists a multitude of pathogens that pose a threat to human and public healthcare, collectively referred to as ESKAPE pathogens. These pathogens are capable of producing biofilm, which proves to be quite resistant to elimination. Strains of A. baumannii, identified by the "A" in the acronym ESKAPE, exhibit significant resistance to amoxicillin in vivo due to their ability to form biofilm. This study aims to inhibit bacterial biofilm formation, evaluate novel silica nanoparticles' effectiveness in inhibiting biofilm, and compare their effectiveness. Amoxicillin was utilized as a positive control, with a concentration exceeding twice that when combined with silica NPs. Treatments included pure silica NPs, silica NPs modified with copper oxide (CuO.SiO2), sodium hydroxide (NaOH.SiO2), and phosphoric acid (H3PO4.SiO2). The characterization of NPs was conducted using scanning electron microscopy (SEM), while safety testing against normal fibroblast cells was employed by MTT assay. The microtiter plate biofilm formation assay was utilized to construct biofilm, with evaluations conducted using three broth media types: brain heart infusion (BHI) with 2% glucose and 2% sucrose, Loria broth (LB) with and without glucose and sucrose, and Dulbecco's modified eagle medium/nutrient (DMEN/M). Concentrations ranging from 1.0 mg/mL to 0.06 µg/mL were tested using a microdilution assay. Results from SEM showed that pure silica NPs were mesoporous, but in the amorphous shape of the CuO and NaOH treatments, these pores were disrupted, while H3PO4 was composed of sheets. Silica NPs were able to target Acinetobacter biofilms without harming normal cells, with viability rates ranging from 61–73%. The best biofilm formation was achieved using a BHI medium with sugar supplementation, with an absorbance value of 0.35. Biofilms treated with 5.0 mg/mL of amoxicillin as a positive control alongside 1.0 mg/mL of each of the four silica treatments in isolation, resulting in the inhibition of absorbance values of 0.04, 0.13, 0.07, 0.09, and 0.08, for SiO2, CuO.SiO2, NaOH.SiO2 and H3PO4.SiO2, respectively. When amoxicillin was combined, inhibition increased from 0.3 to 0.04; NaOH with amoxicillin resulted in the lowest minimum biofilm inhibitory concentration (MBIC), 0.25 µg/mL, compared to all treatments and amoxicillin, whereas pure silica and composite had the highest MBIC, even when combined with amoxicillin, compared to all treatments, but performed better than that of the amoxicillin alone which gave the MBIC at 625 µg/mL. The absorbance values of MBIC of each treatment showed no significant differences in relation to amoxicillin absorbance value and relation to each other. Our study showed that smaller amoxicillin doses combined with the novel silica nanoparticles may reduce toxic side effects and inhibit biofilm formation, making them viable alternatives to high-concentration dosages. Further investigation is needed to evaluate in vivo activity. [ABSTRACT FROM AUTHOR]

Background: Achromobacter spp. is a rare nosocomial pathogen known to cause many serious infections like bloodstream infection, osteomyelitis, meningitis, urinary tract infections, corneal ulceration, peritonitis, and endocarditis. Materials and Methods: In this study, we retrospectively analyzed all the bacteriological sample records from the bacteriology database from January 2021 to December 2021 to determine the prevalence of Achromobacter spp. Result: Nine patients with Achromobacter xylosoxidans causing bacterial infection were identified, from whom five blood samples, two pus, one respiratory sample, one central venous pressure (CVP), and one cerebrospinal fluid were found positive for Achromobacter spp., among whom one was a 6-year-old patient having the same organism from two different body sites—CVP line and cerebrospinal fluid. Five patients had coinfection with another organism, whereas acute kidney injury was the most common comorbidity. Conclusion: In our single-center experience, approximately 50% of the cases with Achromobacter denitrificans bacteremia suffered from chronic kidney disease and had a history of antibiotic therapy, hospitalization, and the presence of devices. Active research on rising trends of Achromobacter spp. needs to be promoted.

ABSTRACT Pseudomonas aeruginosa and Staphylococcus aureus frequently occur together in polymicrobial infections, and there is evidence that their interactions negatively affect disease outcome in patients. At the molecular level, interactions between the two bacterial species are well-described, with P. aeruginosa usually being the dominant species suppressing S. aureus through a variety of inhibitory molecules. However, in chronic infections the two species interact over prolonged periods of time, and S. aureus might be able to evolve resistance against inhibitory molecules deployed by P. aeruginosa. Here, we used experimental evolution to test this hypothesis by exposing three different S. aureus strains (Cowan I, 6850, and JE2) to the growth-inhibitory supernatant of P. aeruginosa PAO1 over 30 days. Prior to evolution, we found that S. aureus strains were inhibited by secreted compounds regulatorily controlled by the Pseudomonas quinolone signal quorum-sensing system. Following evolution, inhibitory effects were significantly attenuated, and we observed that adaptations were S. aureus strain specific and involved the upregulation of virulence traits such as staphyloxanthin production and the formation of small colony variants. At the genetic level, mutations in membrane transporters (known to be involved in antibacterial uptake) were the most frequent evolutionary targets. Our work indicates that adaptations of S. aureus to P. aeruginosa occurs rapidly and affect both virulence trait expression and membrane transporter functionality. Thus, pathogen evolution could promote species co-existence and complicate treatment options in infections. IMPORTANCE Polymicrobial infections are common. In chronic infections, the different pathogens may repeatedly interact, which could spur evolutionary dynamics with pathogens adapting to one another. Here, we explore the potential of Staphylococcus aureus to adapt to its competitor Pseudomonas aeruginosa. These two pathogens frequently co-occur, and P. aeruginosa is seen as the dominant species being able to displace S. aureus. We studied three different S. aureus strains and found that all became quickly resistant to inhibitory compounds secreted by P. aeruginosa. Our experimental evolution revealed strains-specific adaptations with three main factors contributing to resistance evolution: (i) overproduction of staphyloxanthin, a molecule protecting from oxidative stress; (ii) the formation of small colony variants also protecting from oxidative stress; and (iii) alterations of membrane transporters possibly reducing toxin uptake. Our results show that species interactions can change over time potentially favoring species co-existence, which in turn could affect disease progression and treatment options.

Efflux pumps are a specialized tool of antibiotic resistance used by Pseudomonas aeruginosa to expel antibiotics. The current study was therefore conducted to examine the expression of MexAB-OprM and MexCD-OprJ efflux pump genes. In this study, 200 samples were collected from Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC) in Peshawar, Pakistan. All the isolates were biochemically identified by an Analytical Profile Index kit and at the molecular level by Polymerase Chain Reaction (PCR) utilizing specific primers for the OprL gene. A total of 26 antibiotics were tested in the current study using the guidelines of the Clinical and Laboratory Standard Institute (CLSI) and high-level resistance was shown to amoxicillin-clavulanic acid (89%) and low-level to chloramphenicol (1%) by the isolates. The antibiotic-resistant efflux pump genes MexA, MexB, OprM, MexR, MexC, MexD, OprJ, and NfxB were detected in 178 amoxicillin-clavulanic acid-resistant isolates. Mutations were detected in MexA, MexB, and OprM genes but no mutation was found in the MexR gene as analyzed by I-Mutant software. Statistical analysis determined the association of antibiotics susceptibility patterns by ANOVA: Single Factor p = 0.05. The in silico mutation impact on the protein structure stability was determined via the Dynamut server, which revealed the mutations might increase the structural stability of the mutants. The docking analysis reported that MexA wild protein showed a binding energy value of −6.1 kcal/mol with meropenem and the mexA mutant (E178K) value is −6.5 kcal/mol. The mexB wild and mutant binding energy value was −5.7 kcal/mol and −8.0 kcal/mol, respectively. Efflux pumps provide resistance against a wide range of antibiotics. Determining the molecular mechanisms of resistance in P. aeruginosa regularly will contribute to the efforts against the spread of antibiotic resistance globally. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a multidrug-resistant bacterium that has emerged as a significant nosocomial pathogen globally and renowned for its ability to acquire antimicrobial resistance (AMR) genes. However, understanding of its resistance mechanisms to certain drug classes remains limited. This study focused on four bacterial strains (AB863, AB889, AB930, and AB960) exhibiting carbapenem resistance. They demonstrated high minimum inhibitory concentration (MIC) (128 mg/L) to meropenem and were categorized as extensively drug-resistant strains. Subsequently, they were identified as A. baumannii through 16S rRNA gene sequence analysis and species-specific PCR targeting the bla OXA51 -like gene. Three strains were sequenced for their genomes to study the genetic determinants and functional relevance of carbapenem resistance. The draft genome length of the strains ranged from 3.8 to 4.0 Mbp. A total of 16 antibiotic resistance genes including the genes bla OXA-23 and bla OXA-66 which mediate carbapenem resistance were identified in the genomes. A comprehensive multilocus sequence typing analysis involving 95 A. baumannii strains from different Asian countries assigned the four strains to sequence type 2 (ST2), the most predominant ST circulating in Asia. Comparative genome analysis also revealed bla OXA-66 as the most dominant variant of bla OXA-51 -like gene and also a widespread distribution of bla OXA-23 gene. In addition, various mobile genetic elements associated with AMR genes and three efflux pumps families were detected in the genomes of the strains. Transformation of bla OXA-23 and bla OXA-66 genes resulted in meropenem resistance in the transformant which exhibited a MIC of 2 mg/L, thus confirming direct involvement of both genes in carbapenem resistance.

Background/Purpose (s): Nosocomial pathogens can develop biofilms on hospital surfaces and medical devices; however, few studies have focused on the evaluation of mono-and dual-species biofilms developed by nosocomial pathogens under different growth conditions. Methods: This study investigated biofilm development by nosocomial pathogens (Acinetobacter baumannii, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) on biomaterials in different culture media and their components of the extracellular matrix biofilm. Results: The mono-species biofilms showed cell densities from 7.50 to 9.27 Log10 CFU/cm2 on natural rubber latex type I (NLTI) and from 7.58 to 8.79 Log10 CFU/cm2 on stainless steel (SS). Dual-species biofilms consisted of S. aureus + P. aeruginosa (7.87–8.27 Log10 CFU/cm2 in TSBP and TSBME onto SS; p

There exists a multitude of pathogens that pose a threat to human and public healthcare, collectively referred to as ESKAPE pathogens. These pathogens are capable of producing biofilm, which proves to be quite resistant to elimination. Strains of A. baumannii, identified by the “A” in the acronym ESKAPE, exhibit significant resistance to amoxicillin in vivo due to their ability to form biofilm. This study aims to inhibit bacterial biofilm formation, evaluate novel silica nanoparticles’ effectiveness in inhibiting biofilm, and compare their effectiveness. Amoxicillin was utilized as a positive control, with a concentration exceeding twice that when combined with silica NPs. Treatments included pure silica NPs, silica NPs modified with copper oxide (CuO.SiO2), sodium hydroxide (NaOH.SiO2), and phosphoric acid (H3PO4.SiO2). The characterization of NPs was conducted using scanning electron microscopy (SEM), while safety testing against normal fibroblast cells was employed by MTT assay. The microtiter plate biofilm formation assay was utilized to construct biofilm, with evaluations conducted using three broth media types: brain heart infusion (BHI) with 2% glucose and 2% sucrose, Loria broth (LB) with and without glucose and sucrose, and Dulbecco’s modified eagle medium/nutrient (DMEN/M). Concentrations ranging from 1.0 mg/mL to 0.06 µg/mL were tested using a microdilution assay. Results from SEM showed that pure silica NPs were mesoporous, but in the amorphous shape of the CuO and NaOH treatments, these pores were disrupted, while H3PO4 was composed of sheets. Silica NPs were able to target Acinetobacter biofilms without harming normal cells, with viability rates ranging from 61–73%. The best biofilm formation was achieved using a BHI medium with sugar supplementation, with an absorbance value of 0.35. Biofilms treated with 5.0 mg/mL of amoxicillin as a positive control alongside 1.0 mg/mL of each of the four silica treatments in isolation, resulting in the inhibition of absorbance values of 0.04, 0.13, 0.07, 0.09, and 0.08, for SiO2, CuO.SiO2, NaOH.SiO2 and H3PO4.SiO2, respectively. When amoxicillin was combined, inhibition increased from 0.3 to 0.04; NaOH with amoxicillin resulted in the lowest minimum biofilm inhibitory concentration (MBIC), 0.25 µg/mL, compared to all treatments and amoxicillin, whereas pure silica and composite had the highest MBIC, even when combined with amoxicillin, compared to all treatments, but performed better than that of the amoxicillin alone which gave the MBIC at 625 µg/mL. The absorbance values of MBIC of each treatment showed no significant differences in relation to amoxicillin absorbance value and relation to each other. Our study showed that smaller amoxicillin doses combined with the novel silica nanoparticles may reduce toxic side effects and inhibit biofilm formation, making them viable alternatives to high-concentration dosages. Further investigation is needed to evaluate in vivo activity.

Over the last decade, Acinetobacter baumannii has emerged as one of the main causes of infections acquired in the hospital setting. Outbreaks associated with this pathogen are caused mainly due to contamination and transmission in hospital territories. However, the natural habitats of A. baumannii of clinical significance still remain unclear. In this study, we highlight the isolation and identification of multidrug-resistant environmental strains of A. baumannii from the soil of Mangaluru city. All the recovered isolates were biofilm formers, and two isolates were multidrug-resistant and showed resistance to fluoroquinolone, aminoglycosides, sulfonamide, tetracycline, and carbapenems. In addition, they exhibited protease activity, and produced phospholipase C and siderophore. To the best of our knowledge, this is the first study to isolate and identify drug-resistant strains of A. baumannii from the soil. [ABSTRACT FROM AUTHOR]

The number and frequency of multidrug-resistant (MDR) strains as a frequent cause of nosocomial infections have increased, especially for Methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, in part due to device-related infections. The transition to antibiotic-resistance in related bacterial genes and the capability for immune escape have increased the sustainability of biofilms produced by these bacteria. The formation and changes in biofilms have been suggested as a target to prevent or treat staphylococcal infections. Thus, this study reviews the development of candidate staphylococcal vaccines by database searching, and evaluates the immunogenicity and efficacy profiles of bacterial components involved in biofilms. The literature suggests that using common staphylococcal vaccine antigens and multivalent vaccines should further enhance vaccine efficacy.

Efflux pumps are a specialized tool of antibiotic resistance used by Pseudomonas aeruginosa to expel antibiotics. The current study was therefore conducted to examine the expression of MexAB-OprM and MexCD-OprJ efflux pump genes. In this study, 200 samples were collected from Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC) in Peshawar, Pakistan. All the isolates were biochemically identified by an Analytical Profile Index kit and at the molecular level by Polymerase Chain Reaction (PCR) utilizing specific primers for the OprL gene. A total of 26 antibiotics were tested in the current study using the guidelines of the Clinical and Laboratory Standard Institute (CLSI) and high-level resistance was shown to amoxicillin-clavulanic acid (89%) and low-level to chloramphenicol (1%) by the isolates. The antibiotic-resistant efflux pump genes MexA, MexB, OprM, MexR, MexC, MexD, OprJ, and NfxB were detected in 178 amoxicillin-clavulanic acid-resistant isolates. Mutations were detected in MexA, MexB, and OprM genes but no mutation was found in the MexR gene as analyzed by I-Mutant software. Statistical analysis determined the association of antibiotics susceptibility patterns by ANOVA: Single Factor p = 0.05. The in silico mutation impact on the protein structure stability was determined via the Dynamut server, which revealed the mutations might increase the structural stability of the mutants. The docking analysis reported that MexA wild protein showed a binding energy value of −6.1 kcal/mol with meropenem and the mexA mutant (E178K) value is −6.5 kcal/mol. The mexB wild and mutant binding energy value was −5.7 kcal/mol and −8.0 kcal/mol, respectively. Efflux pumps provide resistance against a wide range of antibiotics. Determining the molecular mechanisms of resistance in P. aeruginosa regularly will contribute to the efforts against the spread of antibiotic resistance globally.

Acinetobacter baumannii is an important, opportunistic nosocomial pathogen that causes a variety of nosocomial infections, and whose drug resistance rate has increased in recent years. The CRISPR-Cas system exists in several bacteria, providing adaptive immunity to foreign nucleic acid invasion. This study explores whether CRISPR-Cas is related to drug resistance. Antibiotics were used to treat strains ATCC19606 and AB43, and the expression of CRISPR-related genes was found to be changed. The Csy proteins (Csy1–4) were previously detected to promote target recognition; however, the potential function of csy1 gene is still unknown. Thus, the RecAb homologous recombination system was utilized to knock out the csy1 gene from A. baumannii AB43, which carries the Type I-Fb CRISPR-Cas system, and to observe the drug resistance changes in wild-type and csy1-deleted strains. The AB43Δcsy1 mutant strain was found to become resistant to antibiotics, while the wild-type strain was sensitive to antibiotics. Moreover, transcriptome analysis revealed that the csy1 gene regulates genes encoding CRISPR-Cas-related proteins, drug-resistant efflux pumps, membrane proteins, and oxidative phosphorylation-related proteins, inhibiting antimicrobial resistance in A. baumannii. The in vitro resistance development assay revealed that the complete CRISPR-Cas system could inhibit the development of bacterial resistance. Our findings expand our understanding of the role of CRISPR-Cas csy1 gene in A. baumannii and link the CRISPR-Cas system to the biogenesis of bacterial drug-resistant structures.

Introduction: Vancomycin-resistant enterococci (VRE) are emerging as an important multidrug-resistant pathogen causing nosocomial infections, predominantly bacteremia and urinary tract infections. VRE bacteremia has caused a significant increase in the duration of the hospital stay and mortality and had caused high public health threat due to limited treatment options. Materials and methods: Between October 2017 and September 2020, all consecutive patients with culture-proven bloodstream infection with Enterococcus species, isolated for the first time, were included in the study. A total of 427 Enterococcus species were identified, and antimicrobial susceptibility tests were performed and interpreted using Clinical and Laboratory Standard Institute guidelines. Results: Of the total 427 Enterococcus species isolated, 63 (45.6%) were VRE. Among them, 51/63 (81%) were Enterococcus faecium (E. faecium) and 5/63 (8%) were Enterococcus faecalis. There was an increased trend of VRE rate in the bloodstream infections of 6.12% (2018), 13.2% (2019), and 19.2% (2020). The majority of the VRE patients [43/63 (68%)] were admitted to the intensive care units (ICUs). Vancomycin A (VanA) is the most common phenotype isolated from 51/63(81%) patients. Conclusion: This increasing trend of VRE bacteremia is a red alert to the clinicians and the infection control practitioners, so that strict antibiotic policies and proper adherence to the infection control practices can be initiated to reduce the VRE rate. [ABSTRACT FROM AUTHOR]

To assess the genomic profiles of tigecycline (Tgc)-resistant Acinetobacter baumannii, including antibiotic resistance (AR) genes and virulence factors (VF), whole-genome shotgun sequencing was performed on 19 Tgc-resistant (TgcR) A. baumannii strains collected in a tertiary hospital during the early phase of the clinical introduction of Tgc in China from late 2012 to mid-2014. The major sample types containing TgcR strains were sputum and drain fluid. Data from an average of 624 Mbp of sequence was generated on each bacterial genome, with Q30 quality of 90%, and an average coverage of 96.6%. TCDC-AB0715 was used as a reference genome. The genome sequences were annotated for functional elements including AR genes, VFs, genome islands, and inserted sequences before they were comparatively analyzed. The antibiotic susceptibility phenotypes of the strains were examined by a broth microdilution method to determine the minimal inhibitory concentration (MIC) of strains against major clinical antibiotics. The AR genes (ARGs) were annotated using the Comprehensive Antibiotic Resistance Database (CARD). Thirty-three ARGs were shared by all 19 TgcR strains, and 24 ARGs were distributed differently among strains. A total of 391 VFs were found to be diversely distributed in all TgcR strains. Based on ARG number distribution, the 19 TgcR strains were divided into several groups. Highly differentiated genes included gpi, mphG, armA, msrE, adec, catB8, aadA, sul1, blaOXA–435, aph3i, and blaTEM–1, which may represent gene markers for TgcR A. baumannii sub-types. In addition, when compared with Tgc-sensitive (TgcS) strains collected during the same period, TgcR strains featured enrichment of ARGs including aph6id, aph3ib, and teta. Compared with 26 other whole-genome sequences of A. baumannii deposited in GeneBank, TgcR strains in this study commonly lacked the EF-Tu mutation for elfamycin resistance. Previous investigation of three A. baumannii strains isolated from one patient indicated genomic exchange and a homologous recombination event associated with generation of tigecycline resistance. This study further analyzed additional TgcR strains. Phylogenetic analysis revealed a close evolutionary relationship between 19 TgcR strains and to isolates in East and Northeast China. In short, the comprehensive functional and comparative genomic analysis of 19 clinical TgcR A. baumannii strains isolated in the early stage of Tgc usage in China revealed their close phylogenetic relationship yet variable genetic background involving multiple resistance mechanisms. Using a simple ARG or VF gene number diversity method and marker genes, TgcR strain sub-types can be identified. The distinct characteristics of TgcR A. baumannii strains with versatile genomic resistance and regulation patterns raise concern regarding prediction and control of Tgc resistance in the clinic.

Klebsiella variicola is an emerging pathogen responsible for causing blood-stream infections, urinary and respiratory tract related diseases in humans. In this report, we describe the genome sequence data and phenotypic characterization of K. variicola strain KV093 isolated from India. Comparative genome sequence analysis revealed the presence of genes linked with virulence, iron acquisition and transport, type 1 and type 3 pili, secretion systems including the capsular gene cluster. The plant-associated genes such as nitrogen fixation, growth and defense mechanisms against oxidative stress were also identified. On performing antibiotic susceptibility testing, growth inhibition, and stress challenge assays it was observed that the drug resistant K. variicola KV093 exhibited cross resistance to various antibiotics, antiseptics, including disinfectants. This report highlights the arsenal of virulence and antibiotic resistance determinants in K. variicola KV093, an effort emphasizing the current pressing need for regular surveillance of K. variicola strains especially in India. • Klebsiella variicola is an emerging pathogen of serious concern. • Comparative genome analysis revealed the presence of virulence, plant associated genes and AMR determinants. • Phenotypic characterization showed K. variicola KV093 strain to be antimicrobial resistant and stress tolerant. • This report highlights the need for periodic survivellance of K. variicola from different environments. [ABSTRACT FROM AUTHOR]

To assess the genomic profiles of tigecycline (Tgc)-resistant Acinetobacter baumannii , including antibiotic resistance (AR) genes and virulence factors (VF), whole-genome shotgun sequencing was performed on 19 Tgc-resistant (TgcR) A. baumannii strains collected in a tertiary hospital during the early phase of the clinical introduction of Tgc in China from late 2012 to mid-2014. The major sample types containing TgcR strains were sputum and drain fluid. Data from an average of 624 Mbp of sequence was generated on each bacterial genome, with Q30 quality of 90%, and an average coverage of 96.6%. TCDC-AB0715 was used as a reference genome. The genome sequences were annotated for functional elements including AR genes, VFs, genome islands, and inserted sequences before they were comparatively analyzed. The antibiotic susceptibility phenotypes of the strains were examined by a broth microdilution method to determine the minimal inhibitory concentration (MIC) of strains against major clinical antibiotics. The AR genes (ARGs) were annotated using the Comprehensive Antibiotic Resistance Database (CARD). Thirty-three ARGs were shared by all 19 TgcR strains, and 24 ARGs were distributed differently among strains. A total of 391 VFs were found to be diversely distributed in all TgcR strains. Based on ARG number distribution, the 19 TgcR strains were divided into several groups. Highly differentiated genes included gpi , mphG , armA , msrE , adec , catB8 , aadA , sul1 , bla OXA–435, aph3i , and bla TEM–1, which may represent gene markers for TgcR A. baumannii sub-types. In addition, when compared with Tgc-sensitive (TgcS) strains collected during the same period, TgcR strains featured enrichment of ARGs including aph6id , aph3ib , and teta. Compared with 26 other whole-genome sequences of A. baumannii deposited in GeneBank, TgcR strains in this study commonly lacked the EF-Tu mutation for elfamycin resistance. Previous investigation of three A. baumannii strains isolated from one patient indicated genomic exchange and a homologous recombination event associated with generation of tigecycline resistance. This study further analyzed additional TgcR strains. Phylogenetic analysis revealed a close evolutionary relationship between 19 TgcR strains and to isolates in East and Northeast China. In short, the comprehensive functional and comparative genomic analysis of 19 clinical TgcR A. baumannii strains isolated in the early stage of Tgc usage in China revealed their close phylogenetic relationship yet variable genetic background involving multiple resistance mechanisms. Using a simple ARG or VF gene number diversity method and marker genes, TgcR strain sub-types can be identified. The distinct characteristics of TgcR A. baumannii strains with versatile genomic resistance and regulation patterns raise concern regarding prediction and control of Tgc resistance in the clinic. [ABSTRACT FROM AUTHOR]

The prevalence of multidrug-resistant Gram-negative bacteria is a public health concern. Bacteriophages and bacteriophage-derived lytic enzymes have been studied in response to the emergence of multidrug-resistant bacteria. The availability of tRNAs and endolysin toxicity during recombinant protein expression is circumvented by codon optimization and lower expression levels using inducible pET-type plasmids and controlled cultivation conditions, respectively. The use of polyhistidine tags facilitates endolysin purification and alters antimicrobial activity. Outer membrane permeabilizers, such as organic acids, act synergistically with endolysins, but some endolysins permeate the outer membrane of Gram-negative bacteria per se. However, the outer membrane permeation mechanisms of endolysins remain unclear. Other strategies, such as the co-administration of endolysins with polymyxins, silver nanoparticles, and liposomes confer additional outer membrane permeation. Engineered endolysins comprising domains for outer membrane permeation is also a strategy used to overcome the current challenges on the control of multidrug-resistant Gram-negative bacteria. Metagenomics is a new strategy for screening endolysins with interesting antimicrobial properties from uncultured phage genomes. Here, we review the current state of the art on the heterologous expression of endolysin, showing the potential of bacteriophage endolysins in controlling bacterial infections.

Background and Aim: Acinetobacter baumannii is one of the most important opportunistic pathogen that is responsible of nosocomial infections, especially in intensive care units (ICUs). The prevalence of antibiotic resistant A. baumannii is increasing in world, and this may cause significant clinical problems. Therefore, this study aimed to evaluate the rate of antibiotic resistance of A. baumannii using meta-analysis. Materials and Methods: Information for this study obtained by searching on data bases included: Scopus, PubMed, ISI Web of Science, ISC, SID and Google Scholar by independent researchers using standard keyword and without time limit. Then studies containing inclusion criteria were evaluated. The data were analyzed by using random effects model Meta-analysis method and with the software STATA Ver.12.0. Results and Conclusions: 11 studies were eligible. This studies were analyzed for antibiotics included: cefotaxime, ceftazidime, amikacin, gentamicin, ciprofloxacin and imipenem, based on random effect models. The highest and lowest resistances were found against cefotaxime and imipenem, respectively. This study showed that A. baumannii strain’s have resistance to a wide range of antimicrobial agents. According to the importance of these bacteria in nosocomial infections particularly in intensive care units, it is necessary to apply appropriate strategies to control the spread of this bacteria.

ABSTRACT Enterococcus faecium is a gut commensal of humans and animals but is also listed on the WHO global priority list of multidrug-resistant pathogens. Many of its antibiotic resistance traits reside on plasmids and have the potential to be disseminated by horizontal gene transfer. Here, we present the first comprehensive population-wide analysis of the pan-plasmidome of a clinically important bacterium, by whole-genome sequence analysis of 1,644 isolates from hospital, commensal, and animal sources of E. faecium. Long-read sequencing on a selection of isolates resulted in the completion of 305 plasmids that exhibited high levels of sequence modularity. We further investigated the entirety of all plasmids of each isolate (plasmidome) using a combination of short-read sequencing and machine-learning classifiers. Clustering of the plasmid sequences unraveled different E. faecium populations with a clear association with hospitalized patient isolates, suggesting different optimal configurations of plasmids in the hospital environment. The characterization of these populations allowed us to identify common mechanisms of plasmid stabilization such as toxin-antitoxin systems and genes exclusively present in particular plasmidome populations exemplified by copper resistance, phosphotransferase systems, or bacteriocin genes potentially involved in niche adaptation. Based on the distribution of k-mer distances between isolates, we concluded that plasmidomes rather than chromosomes are most informative for source specificity of E. faecium. IMPORTANCE Enterococcus faecium is one of the most frequent nosocomial pathogens of hospital-acquired infections. E. faecium has gained resistance against most commonly available antibiotics, most notably, against ampicillin, gentamicin, and vancomycin, which renders infections difficult to treat. Many antibiotic resistance traits, in particular, vancomycin resistance, can be encoded in autonomous and extrachromosomal elements called plasmids. These sequences can be disseminated to other isolates by horizontal gene transfer and confer novel mechanisms to source specificity. In our study, we elucidated the total plasmid content, referred to as the plasmidome, of 1,644 E. faecium isolates by using short- and long-read whole-genome technologies with the combination of a machine-learning classifier. This was fundamental to investigate the full collection of plasmid sequences present in our collection (pan-plasmidome) and to observe the potential transfer of plasmid sequences between E. faecium hosts. We observed that E. faecium isolates from hospitalized patients carried a larger number of plasmid sequences compared to that from other sources, and they elucidated different configurations of plasmidome populations in the hospital environment. We assessed the contribution of different genomic components and observed that plasmid sequences have the highest contribution to source specificity. Our study suggests that E. faecium plasmids are regulated by complex ecological constraints rather than physical interaction between hosts.

Acinetobacter baumannii, a Gram-negative bacterium, is an important nosocomial pathogen. Colistin-resistant A. baumannii is becoming a new concern, since colistin is one of the last-line antibiotics for infections by carbapenem-resistant A. baumannii. From 452 carbapenem-resistant isolates collected in a teaching hospital in Taipei, Taiwan, we identified seven that were resistant to colistin. Carbapenem resistance in these isolates is attributed to the presence of carbapenemase gene blaOXA-23 in their genomes. Colistin resistance is presumably conferred by mutations in the sensor kinase domain of PmrB found in these isolates, which are known to result in modification of colistin target lipid A via the PmrB–PmrA–PmrC signal transduction pathway. Overexpression of pmrC, eptA, and naxD was observed in all seven isolates. Colistin resistance mediated by pmrB mutations has never been reported in Taiwan. One of the seven isolates contained three mutations in lpxD and exhibited an altered lipopolysaccharide profile, which may contribute to its colistin resistance. No significant difference in growth rates was observed between the isolates and the reference strain, suggesting no fitness cost of colistin resistance. Biofilm formation abilities of the isolates were lower than that of the reference. Interestingly, one of the isolates was heteroresistant to colistin. Four of the isolates were significantly more virulent to wax moth larvae than the reference.

Acinetobacter baumannii is a worldwide occurring nosocomial pathogen, the natural habitats of which remain to be defined. Recently, white stork nestlings have been described as a recurring source of A. baumannii. Here, we challenged the hypothesis of a general preference of A. baumannii for avian hosts. Taking advantage of campaigns to ring free-living birds, we collected cloacal swab samples from 741 blackheaded gulls (Chroicocephalus ridibundus) in Poland, tracheal and cloacal swabs from 285 songbirds in Poland as well as tracheal swabs from 25 songbirds in Slovenia and screened those for the growth of A. baumannii on CHROMagarTM Acinetobacter. Of the 1,051 samples collected only two yielded A. baumannii isolates. Each carried one variant of the blaOXA-51-like gene, i.e. OXA-71 and OXA-208, which have been described previously in clinical isolates of A. baumannii. In conclusion, our data do not support a general preference of A. baumannii for avian hosts. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter has emerged recently as one of the most challenging nosocomial pathogens because of its increased rate of antimicrobial resistance. The genetic complexity and genome diversity, as well as the lack of adequate knowledge on the pathogenic determinants of Acinetobacter strains often hinder with pathogenesis studies for the development of better therapeutics to tackle this nosocomial pathogen. Objectives: In this study, we comparatively analyzed the whole genome sequence of a virulent Acinetobacternosocomialis strain NCTC 8102. Methods: The genomic DNA of A. nosocomialis NCTC 8102 was isolated and sequenced using PacBio RS II platform. The sequenced genome was functionally annotated and gene prediction was carried out using the program, Glimmer 3. The phylogenetic analysis of the genome was performed using Mega 6 program and the comparative genome analysis was carried out by BLAST (Basic Local Alignment Search Tool). Results: The complete genome analysis depicted that the genome consists of a circular chromosome with an average G + C content of 38.7%. The genome comprises 3700 protein-coding genes, 96 RNA genes (18 rRNA, 74 tRNA and 4 ncRNA genes), and 91 pseudogenes. In addition, 6 prophage regions comprising 2 intact, 1 incomplete and 3 questionable ones and 18 genomic islands were identified in the genome, suggesting the possible occurrence of horizontal gene transfer in this strain. Comparative genome analysis of A. nosocomialis NCTC 8102 genome with the already sequenced A. nosocomialis strain SSA3 showed an average nucleotide identity of 99.0%. In addition, the number of prophages and genomic islands were higher in the A. nosocomialis NCTC 8102 genome compared to that of the strain SSA3. 14 of the genomic islands were unique to A. nosocomialis NCTC 8102 compared to strain SSA3 and they harbored genes which are involved in virulence, multidrug resistance, biofilm formation and bacterial pathogenesis. Conclusion: We sequenced the whole genome of A. nosocomialis strain NCTC 8102 followed by comparatively genome analysis. The study provides valuable information on the genetic features of A. nosocomialis strain and the data from this study would assist in further studies for the development of control measures for this nosocomial pathogen. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa high-risk clones are disseminated worldwide and they are common causative agents of hospital-acquired infections. In this review, we will summarize available data of high-risk P. aeruginosa clones from confirmed outbreaks and based on whole-genome sequence data. Common feature of high-risk clones is the production of beta-lactamases and among metallo-beta-lactamases NDM, VIM and IMP types are widely disseminated in different sequence types (STs), by contrast FIM type has been reported in ST235 in Italy, whereas GIM type in ST111 in Germany. In the case of ST277, it is most frequently detected in Brazil and it carries a resistome linked to blaSPM. Colistin resistance develops among P. aeruginosa clones in a lesser extent compared to other resistance mechanisms, as ST235 strains remain mainly susceptible to colistin however, some reports described mcr positive P. aeurigonsa ST235. Transferable quinolone resistance determinants are detected in P. aeruginosa high-risk clones and aac(6′)-Ib-cr variant is the most frequently reported as this determinant is incorporated in integrons. Additionally, qnrVC1 was recently detected in ST773 in Hungary and in ST175 in Spain. Continuous monitoring and surveillance programs are mandatory to track high-risk clones and to analyze emergence of novel clones as well as novel resistance determinants.

This study analyzed the genotype, antibiotic resistance, and biofilm formation of Acinetobacter baumannii strains and assessed the correlation between biofilm formation, antibiotic resistance, and biofilm-related risk factors. A total of 207 non-replicate multi-drug-resistant A. baumannii strains were prospectively isolated. Phenotypic identification and antimicrobial susceptibility testing were carried out. Isolate biofilm formation ability was evaluated using the tissue culture plate (TCP), Congo red agar, and tube methods. Clonal relatedness between the strains was assessed by enterobacterial repetitive intergenic consensus-PCR genotyping. Of the 207 isolates, 52.5% originated from an intensive care unit setting, and pan resistance was observed against ceftazidime and cefepime, with elevated resistance (99–94%) to piperacillin/tazobactam, imipenem, levofloxacin, and ciprofloxacin. alongside high susceptibility to tigecycline (97.8%). The Tissue culture plate, Tube method, and Congo red agar methods revealed that 53.6%, 20.8%, and 2.7% of the strains were strong biofilm producers, respectively, while a significant correlation was observed between biofilm formation and device-originating respiratory isolates (p = 0.0009) and between biofilm formation in colonized vs. true infection isolates (p = 0.0001). No correlation was detected between antibiotic resistance and biofilm formation capacity, and the majority of isolates were clonally unrelated. These findings highlight the urgent need for implementing strict infection control measures in clinical settings.

Background and Objectives: Hospital-acquired pneumonia (HAP) is a life-threatening hospital-acquired infection contributing to poor outcomes and mortality. Though the prevalence is comparable, the burden of comorbidities and malnutrition further worsens the scenario in developing countries. Infective agents responsible for these infections vary between regions due to the variables involved. There is a dearth of data on clinico-microbiological correlates of HAP from Northern India. With this study, we aim to explore the same and add more evidence to fill the gap., Methodology: A hospital-based cohort study was done on ICU patients of the tertiary care center in Northern India including the cohort of patients obeying a strict inclusion criterion. The clinical and microbiological correlates were estimated following an appraisal of quality of study samples., Results: We found that the most common clinical feature in patients with HAP was fever (82%) followed by purulent respiratory secretions (72%), tachycardia (52%), and crepitations on auscultation (38%). Approximately 86% of cases were found to be culture-positive while others were bacteriologically sterile. Gram-negative bacilli were more commonly isolated (83% Gram-negative vs 17% Gram-positive). The most common organisms isolated were Klebsiella pneumoniae, Citrobacter freundii, Escherichia coli, Acinetobacter, and Pseudomonas aeruginosa. Staphylococcus aureus was isolated from eight specimens and all isolates were susceptible to vancomycin, linezolid, teicoplanin, and tigecycline. Seven isolates were resistant to clindamycin and all 8 were resistant to macrolides and quinolones. Five strains had methicillin resistance indicating a rising burden of 'superbugs'. The most common side involved was the right side and the right middle zone was the most common zone involved. Forty-four percent of cases had a poor outcome and succumbed to the infection., Conclusions: HAP places patients at a heightened risk of mortality and manifests a distinctive clinical-microbiological profile. It is advisable to adopt a proactive stance in averting HAI by adhering to robust prophylaxis and management protocols in alignment with regional data and hospital guidelines. Despite the study's constrained sample size, it contributes significant insights specific to the region. This underscores the necessity for further exploration through analogous studies and audits in the northern part of India. Such endeavors have the potential to tailor treatment approaches for patients, ultimately enhancing overall outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, . et al.)

Photodynamic inactivation (PDI) is a non-invasive and safe therapeutic method for microbial infections. Bacterial antibiotic resistance is caused by antibiotics abuse. Drug-resistant Acinetobacter spp. is a serious problem in hospitals around the world. These pathogens from nosocomial infections have high mortality rates in frailer people, and Acinetobacter spp. is commonly found in immunocompromised patients. Visible light is safer than ultraviolet light (UV) for PDI of nosocomial pathogens with mammalian cells. Zinc oxide nanoparticles (ZnO-NPs) were used in this study as an antimicrobial agent and a photosensitizer. ZnO is recognized as safe and has extensive usage in food additives, medical and cosmetic products. In this study, we used 0.125 mg/ml ZnO-NPs combined with 10.8 J/cm 2 blue light (BL) on Acinetobacter baumannii ( A. baumannii ) that could significantly reduce microbial survival. However, individual exposure to ZnO-NPs does not affect the viability of A. baumannii . BL irradiation could trigger the antimicrobial ability of ZnO nanoparticles on A. baumannii . The mechanism of photocatalytic ZnO-NPs treatment for sterilization occurs through bacterial membrane disruptions. Otherwise, the photocatalytic ZnO-NPs treatment showed high microbial eradication in nosocomial pathogens, including colistin-resistant and imipenem-resistant A. baumannii and Klebsiella pneumoniae . Based on our results, the photocatalytic ZnO-NPs treatment could support hygiene control and clinical therapies without antibiotics to nosocomial bacterial infections. [ABSTRACT FROM AUTHOR]

We describe three types of Pseudomonas aeruginosa pneumonia. Case 1. P. aeruginosa was isolated from the blood and sputum of a 29-year-old male non-smoker who developed severe community-acquired pneumonia (CAP). Piperacillin was initially effective, but fever and lobular pneumonia with cavities developed seven days after discharge. Intravenous piperacillin/tazobactam and tobramycin were administered for four weeks, followed by oral ciprofloxacin for two weeks. He finally recovered, but developed recurrent CAP due to P. aeruginosa despite appropriate antibiotic therapy and immunocompetent status. Case 2. P. aeruginosa was isolated from the blood and sputum of a 57-year-old woman with renal cancer who developed hospital-acquired pneumonia (HAP) after surgical treatment. She recovered after meropenem administration for four weeks. Case 3. A 67-year-old woman with systemic sclerosis and malignant lymphoma who was followed up on an outpatient basis underwent immunosuppressive therapy. Thereafter, she developed pneumonia and was admitted to our institution where P aeruginosa was isolated from blood and sputum samples. Healthcare-associated pneumonia (HCAP) was diagnosed and effectively treated with tobramycin and ciprofloxacin. P. aeruginosa is not only a causative pathogen of HAP and HCAP, but possibly also of CAP.

Background and Aims: Acinetobacter baumannii is one of the most important opportunistic pathogen that is responsible of nosocomial infections, especially in intensive care units (ICUs). The prevalence of antibiotic resistant A. baumannii is increasing in world, and this may cause significant clinical problems. Therefore, this study aimed to evaluate the rate of antibiotic resistance of A. baumannii using meta-analysis. Materials and Methods: Information for this study obtained by searching on data bases included: Scopus, PubMed, ISI Web of Science, ISC, SID and Google Scholar by independent researchers using standard keyword and without time limit. Then studies containing inclusion criteria were evaluated. The data were analyzed by using random effects model Meta-analysis method and with the software STATA Ver.12.0. Results and Conclusions: 11 studies were eligible. This studies were analyzed for antibiotics included: cefotaxime, ceftazidime, amikacin, gentamicin, ciprofloxacin and imipenem, based on random effect models. The highest and lowest resistances were found against cefotaxime and imipenem, respectively. This study showed that A. baumannii strain's have resistance to a wide range of antimicrobial agents. According to the importance of these bacteria in nosocomial infections particularly in intensive care units, it is necessary to apply appropriate strategies to control the spread of this bacteria. [ABSTRACT FROM AUTHOR]

INTRODUCTION: due to an upsurge in antibiotic-resistant infections and lack of therapeutic options, new approaches are needed for treatment. Honey may be one such potential therapeutic option. We investigated the susceptibility of hospital acquired pathogens to four honeys from Wisconsin, United States, and then determined if the antibacterial effect ofeach honey against these pathogensis primarily due to the high sugar content. METHODS: thirteen pathogens including: four Clostridium difficile, two Methicillin-resistant Staphylococcus aureus, two Pseudomonas aeruginosa, one Methicillin-Susceptible Staphylococcus aureus, twoVancomycin-resistance Enterococcus, one Enterococcusfaecalis and one Klebsiella pneumonia were exposed to 1-50% (w/v) four Wisconsin honeys and Artificial honey to determine their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the broth dilution method. RESULTS: buckwheathoney predominantly exhibited a bactericidal mode of action against the tested pathogens, and this varied with each pathogen. C. difficile isolates were more sensitive to the Wisconsin buckwheat honeyas compared to the other pathogens. Artificial honey at 50% (w/v) failed to kill any of the pathogens. The high sugar content of Wisconsin buckwheat honey is not the only factor responsible for its bactericidal activity. CONCLUSION: Wisconsin buckwheat honeyhas the potential to be an important addition to therapeutic armamentarium against resistant pathogens and should be investigated further.

Staphylococcus aureus is one of the major causes of nosocomial infections, pyoarthritis, endocarditis and other disorders. Additionally, the presence of antibiotic-resistant S. aureus especially for methicillin resistant S. aureus (MRSA) is of great concern in medical treatment. This present paper aims to provide fundamental and detailed information of MRSA including morphology, strain distribution, antibiotic-resistant mechanism and means to control MRSA. The potential use of natural products will also be discussed.

Comprehensive data on drug-resistant patterns of Acinetobacter baumannii isolates in developing countries is limited. We conducted a multihospital study to assess the rate and trend of drug-resistant phenotypes in Ac. baumannii using standardized definitions and to determine the remaining therapeutic options against resistant phenotypes. The 401 nonduplicate isolates were collected from six hospitals which are geographically distributed across Tehran, Iran over a 3-year period. Following PCR of bla OXA-51-like gene, susceptibility testing was performed against nine antimicrobial agent categories. Three hundred and ninety (97%) isolates were resistant to least two carbapenems; carbapenem-resistant Ac. baumannii. The majority of isolates (366, 91·3%) were extensively drug resistant ( XDR) and the rest of the isolates were classified as multidrug resistant (26, 6·8%) and susceptible (9, 2·2%). The rate of XDR- AB slightly decreased from 93·8% in 2011 to 89·8% in 2013. A considerable decrease in resistance to doxycycline, minocycline and tigecycline was demonstrated. The XDR- AB isolates showed susceptibility to gentamicin (10·4%), tobramycin (23%), ampicilin-sulbactam (30·1%), minocycline (32·8%), tigecycline (10·7%), doxycycline (21·6%), colistin (100%) and polymixin B (100%). We demonstrated the rising trend of resistance to all antibiotic categories except tetracyclines and folate pathway inhibitors. We found that the treatment options against XDR- AB are extremely limited and each treatment alternative including even old, but safe, antibiotics might be considered. Significance and Impact of the Study The high frequency of drug-resistant phenotypes including carbapenem-resistant Acinetobacter baumannii, multidrug-resistant, and extensively resistant has been demonstrated in Ac. baumannii isolates tested here. As the antibiotic resistance pattern of isolates varies in different geographical regions, this study can provide comprehensive information about the antibiotic resistance profile of Ac. baumannii isolates in Tehran. In addition, the resistance profiles could be effectively considered by clinicians to manage antibiotic therapy. This work also emphasizes on the prudent use of antibiotics and the monitoring of antibiotic susceptibility trend and rate. [ABSTRACT FROM AUTHOR]

Enterococcus faecium, traditionally considered a harmless gut commensal, is emerging as an important nosocomial pathogen showing increasing rates of multidrug resistance. We report the draft genome sequence of E. faecium strain LMG 8148, isolated in 1968 from a human in Gothenburg, Sweden. The draft genome has a total length of 2,697,490 bp, a GC-content of 38.3%, and 2,402 predicted protein-coding sequences. The isolation of this strain predates the emergence of E. faecium as a nosocomial pathogen. Consequently, its genome can be useful in comparative genomic studies investigating the evolution of E. faecium as a pathogen. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a pathogen that is becoming increasingly important and causes serious hospitalacquired infections. We sequenced the genome of A. baumannii NCTC 13423, a multidrug-resistant strain belonging to the international clone II group, isolated from a human infection in the United Kingdom in 2003. The 3,937,944 bp draft genome has a GC-content of 39.0% and a total of 3672 predicted protein-coding sequences. The availability of genome sequences of multidrug-resistant A. baumannii isolates will fuel comparative genomic studies to help understand the worrying spread of multidrug resistance in this pathogen. [ABSTRACT FROM AUTHOR]