Antibiotic-resistant Gram-negative Bacteria Research Articles

Distribution of Microorganisms and Antibiotic Resistance of Gram-negative Bacteria Isolated from Urine Cultures of Intensive Care Unit Patients During the Last Four Years

Distribution of Microorganisms and Antibiotic Resistance of Gram-negative Bacteria Isolated from Urine Cultures of Intensive Care Unit Patients During the Last Four Years

Occurrence and Resistance Pattern of Gram-Negative Bacteremia and Sepsis in A Tertiary Care Hospital - A Four-Year Study

The rise in antibiotic resistance has been a major source of public health concern. As a result, mortality and morbidity rates have risen significantly. This study was done to identify gram-negative organisms causing bacteremia/sepsis, study their prevalence rates, and antimicrobial resistance patterns, as evidence-based knowledge of gram-negative organisms causing sepsis and their resistance profiles is essential for effective hospital control and better management of infections caused by resistant bacteria. A retrospective study, conducted from January 2016 to December 2019, blood samples were collected using aseptic guidelines and cultured using automated blood culture methods. Biochemical tests were done according to microbiology standard procedures, while antimicrobial testing was done according to CLSI guidelines. A total of 13,808 blood samples were received within the study period of four years. Of the total, 2079 showed significant growth, with 765 being GNB isolates. The most common isolates were Escherichia coli (35.42%), Klebsiella pneumonia (19.74%), Acinetobacter species (9.67%), and other non-fermenting gram-negative bacilli (11.76%). Escherichia coli showed yearly resistance to aminoglycosides, cephalosporins, penicillin, fluoroquinolones, and B-lactam combination agents. Routine surveillance and awareness of the prevalence, etiological agents, and antibiotic resistance of gram-negative bacteria causing bacteremia/sepsis is critical for individual therapy, hospital control, and the effectiveness of preventive interventions.

Role of internal loop dynamics in antibiotic permeability of outer membrane porins

Gram-negative bacteria pose a serious public health concern due to resistance to many antibiotics, caused by the low permeability of their outer membrane (OM). Effective antibiotics use porins in the OM to reach the interior of the cell; thus, understanding permeation properties of OM porins is instrumental to rationally develop broad-spectrum antibiotics. A functionally important feature of OM porins is undergoing open-closed transitions that modulate their transport properties. To characterize the molecular basis of these transitions, we performed an extensive set of molecular dynamics (MD) simulations of Escherichia coli OM porin OmpF. Markov-state analysis revealed that large-scale motion of an internal loop, L3, underlies the transition between energetically stable open and closed states. The conformation of L3 is controlled by H bonds between highly conserved acidic residues on the loop and basic residues on the OmpF β-barrel. Mutation of key residues important for the loop's conformation shifts the equilibrium between open and closed states and regulates translocation of permeants (ions and antibiotics), as observed in the simulations and validated by our whole-cell accumulation assay. Notably, one mutant system G119D, which we find to favor the closed state, has been reported in clinically resistant bacterial strains. Overall, our accumulated ∼200 µs of simulation data (the wild type and mutants) along with experimental assays suggest the involvement of internal loop dynamics in permeability of OM porins and antibiotic resistance in Gram-negative bacteria.

Nanoformulations of curcumin and quercetin with silver nanoparticles for inactivation of bacteria.

Antibiotic resistance in pathogenic bacteria to various types of antibiotics has resulted in the necessity of new effective strategies to get around this problem. In recent investigations, metal or metal oxide nanoparticles specifically silver nanoparticles (AgNPs) have been employed successfully to hinder antibiotic-resistant Gram-negative and Gram-positive bacteria. However, AgNPs at high concentrations have cytotoxicity for eukaryotic cells which, application of other biocompatible materials particularly plant secondary metabolites of curcumin and quercetin to reduce cytotoxicity is a critical affair. These compounds may be used directly or indirectly to produce AgNPs. In this regard, modified NPs by curcumin and quercetin have shown an increased therapeutic effect and biocompatibility and biodegredibility properties. Therefore, here, recent advances and challenges about antibacterial and biocompatibility properties of nanoformulation of AgNPs with curcumin and quercetin are presented.

Sensitization of Antibiotic-Resistant Gram-Negative Bacteria to Photodynamic Therapy via Perfluorocarbon Nanoemulsion.

With the merits of excellent efficacy, safety, and facile implementation, antibacterial photodynamic therapy (APDT) represents a promising means for treating bacterial infections. However, APDT shows an unsatisfactory efficacy in combating antibiotic-resistant Gram-negative bacteria due to their specific cell wall structure. In this work, we report a perfluorocarbon nanoemulsion (Ce6@FDC) used as a multifunctional nanocargo of photosensitizer and oxygen for sensitizing antibiotic-resistant Gram-negative bacteria to APDT. Ce6@FDC was fabricated via ultrasonic emulsification with good colloidal stability, efficient Ce6 and oxygen delivery, and excellent photodynamic activity. Meanwhile, Ce6@FDC could strongly bind with Gram-negative Acinetobacter baumannii (A. baumannii) and Escherichia coli (E. coli) via electrostatic interaction, thus leading to notable photodynamic bactericidal potency upon irradiation. In addition, oxygenated Ce6@FDC also exhibited a remarkable efficacy in eradicating Gram-negative bacteria biofilm, averaging five log units lower than the Ce6 group under identical conditions. Taken together, we demonstrate that photodynamic perfluorocarbon nanoemulsion with oxygen-delivery ability could effectively kill planktonic bacteria and remove biofilm, representing a novel strategy in fighting against antibiotic-resistant Gram-negative bacteria.

Antibacterial activity and cytotoxicity of bioinspired poly(L-DOPA)-mediated silver nanostructure-decorated titanium dioxide nanowires

The combination of silver (Ag) and titanium dioxide (TiO2) nanostructures offer unique advantages in terms of elimination of infection and enhanced antibacterial activity with relatively higher biocompatibility and lower cytotoxicity. Although there have been numerous attempts for the fabrication of these nanocomposite systems, novel, flexible, low-cost, simple, effective, reducing, and stabilizing agent-free strategies are highly required for biomedical applications. Within this context, we report the employment of silver nanostructure decorated TiO2 nanowires (TiO2 NWs) as an ideal antibacterial agent against antibiotic-resistant Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Firstly, TiO2 NWs were fabricated via the hydrothermal procedure. Afterward, by utilizing the oxidative polymerization of 3,4-dihydroxyphenyl-L-alanine (L-DOPA), a conformal and thin polymer layer of L-DOPA (PLDP) was created onto the TiO2 NWs (TiO2/PLDP). Lastly, Ag nanostructures were deposited onto the TiO2/PLDP (TiO2/PLDP/Ag NP) via simply reduction of silver ions. Herein, PLDP with its abundant catechol and amine groups played an important role in the reduction of silver ions and the adsorption of Ag nanostructures with high affinity and resultant stability. The size, density, and morphology of Ag nanostructures were manipulated by tuning the initial amount of Ag ions in a well-controlled manner. The resultant colloidal TiO2/PLDP/Ag composite nanosystem provided remarkably high and stable antibacterial activity against both antibiotic-resistant bacteria strains. Minimum Inhibitory Concentration (MIC) values were found to be 125, 250, and > 500 ppm for high, medium and, low deposition of Ag nanostructures, respectively. Similarly, Minimum Bactericidal Concentration (MBC) for these NP systems, MBC values were found to be 250, 500, and > 1000 ppm, respectively. Also, relatively lower cytotoxicity in human lung healthy (MRC5) and cancer (A549) cell lines was detected in a dose-dependent manner in comparison to the citrate-stabilized Ag nanoparticles. The proposed novel TiO2/PLDP/Ag nanosystem will provide unique opportunities in terms of flexibility, low-cost, simplicity with reducing, and stabilizing agent-free strategy and be employed in the removal of biofilms and anti-inflammatory effects.

Design and evaluation of poly-nitrogenous adjuvants capable of potentiating antibiotics in Gram-negative bacteria.

Antibiotic resistance has been a growing public health crisis since the 1980s. Therefore, it is essential not only to continue to develop novel antibiotics but also to develop new methods for overcoming resistance mechanisms in pathogenic bacteria so antibiotics can be reactivated towards these resistant strains. One common cause of antibiotic resistance in Gram-negative bacteria is reduced permeability of the tightly packed, negatively charged lipopolysaccharide outer membrane (OM), which dramatically reduces or even prevents antibiotic accumulation within the cell. Adjuvants that promote passive diffusion through the OM, including phenylalanine-arginine-β-naphthylamide, tobramycin, and pentamidine, have proven useful in potentiating antibiotics against Gram-negative bacteria. Structural evaluation of these adjuvants, which all include multiple nitrogenous groups, indicates that the entry rules developed for improving antibiotic accumulation in Escherichia coli (EC), could also be used to guide adjuvant development. To this end, a series of structurally simple poly-nitrogenous diphenylsuccinamide compounds have been prepared and evaluated for their ability to potentiate a panel of classic antibiotics in wild-type EC and Pseudomonas aeruginosa (PA). Modest adjuvant activity was observed for all compounds surveyed when co-administered with known antibiotics to inhibit either wild-type EC or PA, and all were able to accumulate in both EC and PA.

Antibiotic exposure and acquisition of antibiotic-resistant gram-negative bacteria among outpatients at a US Veterans Affairs medical center.

To assess the prevalence of antibiotic-resistant gram-negative bacteria (R-GNB) among patients without recent hospitalization and to examine the influence of outpatient antibiotic exposure on the risk of acquiring R-GNB in this population. 2-year retrospective cohort study. Regional Veterans Affairs healthcare system. Outpatients at 13 community-based clinics. We examined the rate of acquisition of R-GNB within 90 days following an outpatient visit from 2018 to 2019. We used clinical and administrative databases to determine and summarize prescriptions for systemic antibiotics, associated infectious diagnoses, and subsequent R-GNB acquisition among patients without recent hospitalizations. We also calculated the odds ratio of R-GNB acquisition following antibiotic exposure. During the 2-year study period, 7,215 patients had outpatient visits with microbiological cultures obtained within 90 days. Of these patients, 206 (2.9%) acquired an R-GNB. Among patients receiving antibiotics at the visit, 4.6% acquired a R-GNB compared to 2.7% among patients who did not receive antibiotics, yielding an unadjusted odds ratio of 1.75 (95% confidence interval, 1.18-2.52) for a R-GNB following an outpatient visit with versus without an antibiotic exposure. Regardless of R-GNB occurrence, >50% of antibiotic prescriptions were issued at visits without an infectious disease diagnosis or issued without documentation of an in-person or telehealth clinical encounter. Although the rate of R-GNBs was low (2.9%), the 1.75-fold increased odds of acquiring a R-GNB following an outpatient antibiotic highlights the importance of antimicrobial stewardship efforts in outpatient settings. Specific opportunities include reducing antibiotics prescribed without an infectious diagnosis or a clinical visit.

Vegetables and Fruit as a Reservoir of β-Lactam and Colistin-Resistant Gram-Negative Bacteria: A Review.

Antibacterial resistance is one of the 2019 World Health Organization’s top ten threats to public health worldwide. Hence, the emergence of β-lactam and colistin resistance among Gram-negative bacteria has become a serious concern. The reservoirs for such bacteria are increasing not only in hospital settings but in several other sources, including vegetables and fruit. In recent years, fresh produce gained important attention due to its consumption in healthy diets combined with a low energy density. However, since fresh produce is often consumed raw, it may also be a source of foodborne disease and a reservoir for antibiotic resistant Gram-negative bacteria including those producing extended-spectrum β-lactamase, cephalosporinase and carbapenemase enzymes, as well as those harboring the plasmid-mediated colistin resistance (mcr) gene. This review aims to provide an overview of the currently available scientific literature on the presence of extended-spectrum β-lactamases, cephalosporinase, carbapenemase and mcr genes in Gram-negative bacteria in vegetables and fruit with a focus on the possible contamination pathways in fresh produce.

Bad bugs: antibiotic-resistant bacteriuria in pregnancy and risk of pyelonephritis

The introduction of antibiotics has significantly reduced morbidity and mortality from microbial infections, but the rise of antibiotic-resistant and multidrug-resistant microbes is of increasing clinical concern. Few studies have examined the prevalence and impact of antibiotic resistance in common antenatal infections. This study aimed to determine whether pregnant women with a urine culture positive for antibiotic-resistant or multidrug-resistant gram-negative bacteria are at increased risk of developing pyelonephritis than pregnant women infected with antibiotic-susceptible organisms. This was a retrospective cohort study of pregnant women with asymptomatic bacteriuria or acute cystitis from a single health system from July 2013 to May 2019. Women with gram-negative antibiotic-resistant (resistance to 1-2 antibiotic classes) and multidrug-resistant (resistance to ≥3 antibiotic classes) lower urinary tract infections were compared with women with antibiotic-susceptible urinary tract infections in terms of demographic, infectious, antepartum, and intrapartum data. The primary outcome was pyelonephritis, defined as a billing code for pyelonephritis plus fever or flank pain. The secondary outcomes were length of stay in the hospital because of pyelonephritis, a composite of pyelonephritis complications (renal abscess, sepsis, and intensive care unit admission), and preterm delivery. The differences in the primary outcome were analyzed using multivariate logistic regression. A total of 573 women were eligible for inclusion. Of the 573 women, 334 (58%) had gram-negative bacteria on urine culture. Of the 334 cases, 173 (52%) were antibiotic susceptible, 74 (22%) were antibiotic resistant, and 87 (26%) were multidrug resistant. Women with antibiotic-resistant and multidrug-resistant infections were more likely to have hypertension (P=.004), to be Black (P=.03), to have public insurance (P=.002), and to experience more urinary infections (P=.001). Pyelonephritis was more common in women with antibiotic-resistant (adjusted odds ratio, 2.27; 95% confidence interval, 1.08-4.78) and multidrug-resistant (adjusted odds ratio, 3.06; 95% confidence interval, 1.57-5.96) infections than in women with antibiotic-susceptible urinary tract infections. Length of stay, preterm delivery, and pyelonephritis complications did not differ between antibiotic-susceptible and antibiotic-resistant and multidrug-resistant infections. In an age of increasing antibiotic resistance, more than one-half of pregnant women with bacteriuria experience at least 1 infection with an antibiotic-resistant organism. These resistance patterns have a real clinical impact as pregnant women with antibiotic-resistant gram-negative lower urinary tract infections have an estimated 2- to 3-fold increased odds of developing pyelonephritis.

Integron detection for prediction of trimethoprim/sulfamethoxazole susceptibility in children with Enterobacterales urinary tract infections.

In some countries, third-generation cephalosporins (3GCs) serve as first-line therapy in children with urinary tract infections (UTIs). However, their use may contribute to the emergence of antibiotic resistance, notably among Gram-negative bacteria (GNB). Integrons are bacterial genetic elements involved in antibiotic resistance in GNB. Their absence is associated with >97% susceptibility to trimethoprim/sulfamethoxazole in adults infected with GNB. The objective of this study was to examine the value of integron detection directly from urine samples as a predictive marker of resistance to trimethoprim/sulfamethoxazole in children with GNB-related UTIs. Children admitted to the Limoges University Hospital's paediatric emergency department between February 2018 and March 2019 with a suspicion of UTI were eligible for the study. Only confirmed cases presenting a positive urine culture with unique GNB were retained for further study analyses. Integrons were detected directly from urines using real-time PCR. The data of 72 patients were analysed and integrons were detected in 15 urine samples. The negative predictive value of integron detection for resistance to trimethoprim/sulfamethoxazole was 100% as all of the GNB (all were Enterobacterales) isolated from patients with no integrons detected in their urine samples were susceptible to trimethoprim/sulfamethoxazole. The detection of integrons in cases of paediatric patients with suspected UTI could help limit 3GC empirical use and empower an empirical first-line strategy better tailored to the needs of each patient.

Intrinsic Antimicrobial Peptide Facilitates a New Broad-Spectrum Lysin LysP53 to Kill Acinetobacter baumannii In Vitro and in a Mouse Burn Infection Model

Antimicrobial resistance-related infections of Gram-negative pathogens pose a huge threat to global public health. Lysins, peptidoglycan hydrolases from bacteriophages, are expected as an alternative weapon against drug-resistant bacteria. In the present study, we report a new lysin LysP53 from Acinetobacter baumannii phage 53. Bioinformatic analysis revealed that LysP53 contains a positively charged N-terminal region and a putative peptidase catalytic domain. In vitro biochemical experiments showed that LysP53 is active against multiple antibiotic-resistant Gram-negative bacteria, including A. baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, with a reduction of 5 logs in viable A. baumannii number after exposure to 100 μg/mL LysP53 for 1 h. Further studies showed that LysP53 contains a functional antimicrobial peptide, i.e., N-terminal 33 aa, with a comparable spectrum of activity to LysP53. In an A. baumannii-associated mouse model of burn infection, a single dose of 14 μg/mouse LysP53 (57.6 μM) showed higher decolonization efficacy than 4 μg/mouse minocycline- (874 μM; p < 0.05) and buffer-treated groups (p <0.001), leading to a bacterial reduction of 3 logs. Our findings collectively establish that LysP53 could be a promising candidate in the treatment of topical infections caused by multiple Gram-negative pathogens.

In situ Forming Hyperbranched PEG-Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties.

The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol–ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0–1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0–1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0–500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care.

Antibiotic-resistant Gram-negative Bacteria in Urban Flies, and the Increased Risk Posed by Open-air Markets in Mexico City

Aims: Flies are known to spread antibiotic resistant bacteria (ARB), especially from farms to cities; but they may also play a role in the intra-urban dispersion of ARB, in conjunction with poor sanitary conditions. Here, we characterized gram-negative ARB isolated from urban flies (Lucilia and Sarcophaga spp.), and the co-relation with the periodic installation of two open-air markets in Mexico City.&#x0D; Methodology: Forty-two flies were individually captured, and 116 gram-negatives (68 of them Escherichia coli) were isolated from them. Resistance prevalence, and the presence of class 1 integrons was assessed.&#x0D; Results: The isolates were resistant to an average of 2.26 antibiotics (2.6 for E. coli), and 33% of E. coli isolates carried the intI1 gene. Thirteen percent of E. coli isolates produced extended-spectrum beta-lactamases (ESBL), all of them CTX-M, alone or, mostly, along TEM enzymes. Comparing data from market-free days vs. days when open-air markets were installed, the average number of resistance phenotypes per E. coli isolate went from 2.14 to 3.09; the number of resistance phenotypes per fly from 4.62 to 8.88; the average number of resistances per isolate per fly from 1.25 to 2.43; and the ESBL-producing carriage rate per fly from 0.08 to 0.38, respectively (P &lt;.05). Other resistance parameters, were consistently higher among flies captured on market days, but differences were not significant.&#x0D; Conclusion: Urban flies in Mexico City carry a high number of gram-negative ARB; the presence of open-air markets significantly increase the risk of fly-mediated ARB spreading to the neighboring areas.

The antimicrobial effect of 400nm femtosecond laser and silver nanoparticles on gram-positive and gram-negative bacteria.

Silver nanoparticles are well-known for their antimicrobial effect. However, they are potentially toxic in high doses. We explored the possibility of enhancing the bactericidal effect of low concentrations of silver nanoparticles with blue light femtosecond laser irradiation, since such concentrations are less toxic. The growth dynamics of Pseudomonas aeruginosa, Listeria monocytogenes and methicillin-resistant Staphylococcus aureus grown in pre-synthesized silver nanoparticles were measured with or without pre-irradiation with 50mW and 400nm femtosecond laser irradiation. With each bacterium, combined treatment with laser and silver nanoparticles significantly reduced bacterial growth, indicating that this form of treatment could be beneficial in the ongoing efforts to reduce the deleterious effects of antibiotic resistant Gram-positive and Gram-negative bacteria. The combined treatment was more antimicrobial than treatment with silver nanoparticles alone or photo-irradiation alone. P. aeruginosa and L. monocytogenes were more susceptible to the bactericidal effects of silver nanoparticles, and the combination of laser treatment and silver nanoparticles than MRSA.

PREPARATION AND CHARACTERISATION OF NEW BIOMATERIALS BASED ON CHITOSAN IODIDE WITH BIOLOGICALLY ACTIVE DYES

New composite materials were obtained based on chitosan iodide and organic dyes – methylene blue and fuchsine in fucorcin (Castellani liquid) – by using a simple synthetic procedure. The materials were characterised by scanning electron microscopy, X-ray diffraction, temperature-programmed desorption mass spectrometry, infrared spectroscopy and visible and ultraviolet light spectroscopy. The dyes in the composites were distributed uniformly and did not form separate phases. These composites could form structured porous sponges and films and therefore be used in various fields of application. The materials displayed antibacterial activity against antibiotic resistant gram-positive and gram-negative bacteria.

Light-activated disinfection in endodontics: A comprehensive review

Light-activated disinfection (LAD) has emerged as a novel approach toward antimicrobial disinfection within the root canal. This approach is based on the concept that porphyrins and photosensitizers (PSs) can be activated by light to produce cytotoxic elements that induce the desired therapeutic effect. Unlike antibiotics, LAD can act on multiple targets within a bacterial cell, including membrane lipids, genomic DNA and various proteins, including enzymes, thus reducing the ability of the organism to acquire resistance.The aim of this review was to develop an understanding of the potential use of LAD in endodontics and to suggest strategies to maximize the antibacterial effects of LAD.The electronic searches of the PubMed/MEDLINE, Web of Science, Scopus, and Cochrane databases were complemented by a manual hand search. A total of 303 studies were evaluated for essential parameters, which included the origin, types/variations, methodology, and application of LAD in in vitro and in vivo studies.It can be concluded that LAD is effective against the vast majority of bacterial pathogens, including antibioticresistant Gram-negative and Gram-positive bacteria, along with several yeasts, viruses and protozoan species. The literature tends to suggest that LAD can be used either as a substitute or an adjunct to the conventional antimicrobial treatment regimens that are implemented to battle polymicrobial biofilms.

Pseudomonas aeruginosa as a priority group representative of bacteria with multiple antibiotic resistance

The aim: the aim of the research is an analytical review of the scientific literature on Рseudomonas aeruginosa as a priority group representative of bacteria with multiple antibiotics resistance.&#x0D; Materials and methods. The research was conducted by the method of scientific literature open source analysis: PubMed, Elsevier, electronic resources of the National Library named after V. I. Vernadsky and others.&#x0D; Results. The problem of antibiotic resistance is rightly called the “apocalypse of the XXI century”.&#x0D; P. aeruginosa bacteria are characterized by a very high natural ability to form resistant forms to antimicrobial drugs due to the formation of specific resistance genes, the ability to resist the entry of antibiotics into the cell or remove antibiotics from the cell, and form biofilms.&#x0D; A characteristic feature of the epidemic and epizootic processes of P. aeruginosa, as an opportunistic ubiquitous microorganism is host-pathogenic interaction - the interaction of the pathogen with the host organism. The peculiarity of this bacterium is opportunism and long-term persistence in the body of the host and in the environment.&#x0D; The global trend towards the spread of antibiotic-resistant gram-negative bacteria, including P. aeruginosa, underscores the need to develop comprehensive response strategies targeting all sectors of health.&#x0D; Conclusions. Bacteria P. aeruginosa is classified in 1th Critical Group of the WHO list of resistant to antibiotics "priority pathogens". Among the main reasons that contribute to the emergence of resistance are irrational antibiotic therapy in both humans and animals, and the use of antibiotics as growth stimulants in animal husbandry.&#x0D; While more R&amp;D is vital, alone, it cannot solve the problem. To address resistance, there must also be better prevention of infections and appropriate use of existing antibiotics in humans and animals, as well as rational use of any new antibiotics that are developed in future.&#x0D; New methods of combating antibiotic resistance and antibacterial substances, alternatives to antibiotics (biofilm-destroying drugs, antimicrobial peptides (AMP), bacteriophages, nanopreparations, etc.) can make a positive contribution to overcoming the multiple drug resistance of gram-negatives

Integrons, a predictive biomarker for antibiotic resistance in acute sepsis: the IRIS study.

Considering the increase in MDR Gram-negative bacteria (GNB), the choice of empirical antibiotic therapy is challenging. In parallel, use of broad-spectrum antibiotics should be avoided to decrease antibiotic selection pressure. Accordingly, clinicians need rapid diagnostic tools to narrow antibiotic therapy. Class 1-3 integrons, identified by intI1-3 genes, are genetic elements that play a major role in antibiotic resistance in GNB. The objective of the IRIS study was to evaluate the negative and positive predictive values (NPVs and PPVs, respectively) of intI1-3 as markers of antibiotic resistance. The IRIS study was an observational cross-sectional multicentre study that enrolled adult subjects with suspected urinary tract or intra-abdominal infections. intI1-3 were detected directly from routinely collected biological samples (blood, urine or intra-abdominal fluid) using real-time PCR. A patient was considered 'MDR positive' if at least one GNB, expressing acquired resistance to at least two antibiotic families among β-lactams, aminoglycosides, fluoroquinolones and/or co-trimoxazole, was isolated from at least one biological sample. Over a 2 year period, 513 subjects were enrolled and 409 had GNB documentation, mostly Enterobacterales. intI1 and/or intI2 were detected in 31.8% of patients and 24.4% of patients were considered 'MDR positive'. The NPV of intI1 and/or intI2 as a marker of acquired antibiotic resistances was estimated at 92.8% (89.1%-95.5%). The NPVs for first-line antibiotics were all above 92%, notably >96% for resistance to third-generation cephalosporins. The IRIS study strongly suggests that the absence of intI1 and intI2 in biological samples from patients with GNB-related infections is predictive of the absence of acquired resistances.

Co-infection of ST2IP carbapenem-resistant Acinetobacter baumannii with SARS-CoV-2 in the patients admitted to a Tehran tertiary referral hospital

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) is among the most concerning cause of healthcare-associated infections (HAI) due to its high level of antibiotic resistance and high mortality. In the era of the COVID-19 pandemic, the key priority of infection control committees is to contain the dissemination of antibiotic resistant Gram-negative bacteria. Here, we aimed to timely recognize the emergence of CRAB in COVID-19 cases admitted to the wards of a tertiary referral hospital and to identify the genetic relatedness of the isolates.MethodsFrom 30 March to 30 May 2020, a total of 242 clinical samples from COVID-19 cases were screened for CRAB isolates using standard microbiologic and antibiotic susceptibility tests. The PCRs targeting oxa23, oxa24, oxa58, blaTEM and blaNDM-1 genes were performed. Two multiplex PCRs for identifying the global clones (GC) of A. baumannii were also performed. The sequence type of CRABs was determined using Institut Pasteur (IP) multilocus sequence typing (MLST) scheme.ResultsEighteen CRAB isolates were recovered from COVID-19 patients with the mean age of 63.94 ± 13.8 years. All but 4 COVID-19 patients co-infected with CRAB were suffering from an underlying disease. Death was recorded as the outcome in ICUs for 9 (50%) COVID-19 patients co-infected with CRAB. The CRAB isolates belong to GC2 and ST2IP and carried the oxa23 carbapenem resistance gene.ConclusionThis study demonstrated the co-infection of CRAB isolates and SARS-CoV-2 in the patients admitted to different ICUs at a referral hospital in Tehran. The CRAB isolates were found to belong to ST2IP, share the oxa23 gene and to have caused several outbreaks in the wards admitting COVID-19 patients.