The burden of antibiotic resistance of the main microorganisms causing infections in humans - review of the literature.

One of the biggest threats to human well-being and public health is antibiotic resistance. If allowed to spread unchecked, it might become a major health risk and trigger another pandemic. This proves the need to develop antibiotic resistance-related global health solutions that take into consideration microdata from various global locations. Establishing positive social norms, guiding individual and group behavioral habits that support global human health, and ultimately raising public awareness of the need for such action could all have a positive impact. Antibiotic resistance is not just a growing clinical concern but also complicates therapy, making adherence to current guidelines for managing antibiotic resistance extremely difficult. Numerous genetic components have been connected to the development of resistance; some of these components have intricate paths of transfer between microorganisms. Beyond this, the subject of antibiotic resistance is becoming increasingly significant in medical microbiology as new mechanisms underpinning its development are identified. In addition to genetic factors, behaviors such as misdiagnosis, exposure to broad-spectrum antibiotics, and delayed diagnosis contribute to the development of resistance. However, advancements in bioinformatics and DNA sequencing technology have completely transformed the diagnostic sector, enabling real-time identification of the components and causes of antibiotic resistance. This information is crucial for developing effective control and prevention strategies to counter the threat.

Multidrug-resistant tuberculosis in middle ear: A case report.

Background: Tuberculosis (TB) continues to be a common disease in developing countries, among which middle ear TB is rare. Furthermore, it is relatively difficult to make an early diagnosis and provide follow-up treatment for middle ear TB. So, it is necessary to report this case for reference and further discussion. Case presentation: We reported 1 case of multidrug-resistant tuberculosis otitis media. TB otitis media is rare in tuberculosis; multidrug-resistant TB otitis media is even more rare. Our paper analyzes the possible causes, imaging, molecular biology, pathology, and clinical manifestations of multidrug-resistant TB otitis media. Conclusion: PCR and DNA molecular biology techniques are highly recommended for the early diagnosis of multidrug-resistant TB otitis media. Early, effective anti-tuberculosis treatment is the guarantee for further recovery for patients with multidrug-resistant TB otitis media.

Infection prevention and control programme and COVID-19 measures: Effects on hospital-acquired infections in patients with cirrhosis.

Background & Aims: Bacterial infections affect survival of patients with cirrhosis. Hospital-acquired bacterial infections present a growing healthcare problem because of the increasing prevalence of multidrug-resistant organisms. This study aimed to investigate the impact of an infection prevention and control programme and coronavirus disease 2019 (COVID-19) measures on the incidence of hospital-acquired infections and a set of secondary outcomes, including the prevalence of multidrug-resistant organisms, empiric antibiotic treatment failure, and development of septic states in patients with cirrhosis. Methods: The infection prevention and control programme was a complex strategy based on antimicrobial stewardship and the reduction of patient's exposure to risk factors. The COVID-19 measures presented further behavioural and hygiene restrictions imposed by the Hospital and Health Italian Sanitary System recommendations. We performed a combined retrospective and prospective study in which we compared the impact of extra measures against the hospital standard. Results: We analysed data from 941 patients. The infection prevention and control programme was associated with a reduction in the incidence of hospital-acquired infections (17 vs. 8.9%, p <0.01). No further reduction was present after the COVID-19 measures had been imposed. The impact of the infection prevention and control programme remained significant even after controlling for the effects of confounding variables (odds ratio 0.44, 95% CI 0.26-0.73, p = 0.002). Furthermore, the adoption of the programme reduced the prevalence of multidrug-resistant organisms and decreased rates of empiric antibiotic treatment failure and the development of septic states. Conclusions: The infection prevention and control programme decreased the incidence of hospital-acquired infections by nearly 50%. Furthermore, the programme also reduced the prevalence of most of the secondary outcomes. Based on the results of this study, we encourage other liver centres to adopt infection prevention and control programmes. Impact and implications: Infections are a life-threatening problem for patients with liver cirrhosis. Moreover, hospital-acquired infections are even more alarming owing to the high prevalence of multidrug-resistant bacteria. This study analysed a large cohort of hospitalised patients with cirrhosis from three different periods. Unlike in the first period, an infection prevention programme was applied in the second period, reducing the number of hospital-acquired infections and containing multidrug-resistant bacteria. In the third period, we imposed even more stringent measures to minimise the impact of the COVID-19 outbreak. However, these measures did not result in a further reduction in hospital-acquired infections.

Phenotypic and genotypic characterization of clinical Pseudomonas aeruginosa.

Objectives: Pseudomonas aeruginosa is an opportunistic pathogen that can cause many nosocomial infections. Biofilm formation, drug resistance, and motility contribute to virulence in P. aeruginosa. This study assessed the colistin minimum inhibitory concentration (MIC), biofilm formation, presence of mod A and psl A genes, and types of motilities in multidrug-resistant (MDR) and multidrug-susceptible (MDS) P. aeruginosa. Methods: Sixty-two P. aeruginosa from pus and 18 from urine samples were studied for their susceptibility to commonly used antibiotics, colistin MIC by agar dilution, and biofilm-forming ability by the microtiter plate method. All MDR and MDS P. aeruginosa isolates were tested for the presence of mod A and psl A genes by PCR, and different types of motilities using specific media. Results: Among the 40 MDR and 40 MDS isolates, 17 each were colistin-resistant and 23 each were colistin-intermediate. Nine MDR pus isolates and three MDR urine isolates showed all three types of motilities. Thirteen MDS pus isolates and four MDS urine isolates showed both swimming and swarming motility. MDS isolates did not show twitching motility. A higher number of MDR strains were strong biofilm producers (n = 19), whereas a higher number of MDS strains (n = 24) were moderate biofilm producers (p = 0.023). Twenty-seven MDR and twenty-eight MDS isolates were positive for both mod A and pslA genes. Among the strong biofilm-forming pus isolates, a greater number of MDR isolates (n = 13 each) had modA and pslA genes compared to MDS isolates (modA p = 0.017; pslA p = 0.014). Conclusions: Our findings clearly showed a statistically significant association among strong biofilm formation, modA, pslA genes, and drug resistance in P. aeruginosa isolated from clinical samples. Additional studies are needed to explore other genes and factors responsible for weak and moderate biofilm formation and drug resistance.

Biofilm-forming microorganisms causing hospital-acquired infections from intravenous catheter: A systematic review.

The high prevalence of nosocomial infections is related to the use of medical insertion devices such as central venous catheters (CVCs). Most of the microorganisms causing nosocomial infections are biofilm producers, this characteristic allows them to adhere to abiotic surfaces and cause initial catheter infections that can lead to bloodstream infections. Our main goal in this systematic review was to evaluate the prevalence of biofilm among CVC-related infections, particularly among Intensive Care Unit (ICU) patients, in the studies applying different in vitro and in vivo methodologies. All studies reporting clinical isolates from patients with catheter-related nosocomial infections and biofilm evaluation published up to 24 June 2022 in the PubMed and Scopus databases were included. Twenty-five studies met the eligibility criteria and were included in this systematic review for analysis. Different methodologies were applied in the assessment of biofilm-forming microorganisms including in vitro assays, catheter-infected in vitro, and in vivo mouse models. The present study showed that between 59 and 100% of clinical isolates were able to form biofilms, and the prevalence rate of biofilm formation varied significantly between studies from different countries and regions. Among the clinical isolates collected in our study set, a wide variety of microorganisms including Gram-positive strains, Gram-negative strains, and Candida albicans were found. Many authors studied resistance mechanisms and genes related to biofilm development and surface adherence properties. In some cases, the studies also evaluated biofilm inhibition assays using various kinds of catheter coatings.

Antibiogram, prevalence of methicillin-resistant and multi-drug resistant Staphylococcus spp. in different clinical samples.

Methicillin-resistant Staphylococcus spp. (MRSS) are causing numerous forms of illness in humans ranging from mild to fatal infections. We need to investigate the resistant pattern for different clinical isolates to control the resistance phenomena. This study was designed to provide the resistance pattern of isolated Staphylococcus spp. from various clinical samples in Khartoum State and to elucidate the frequencies of Multidrug-resistant (MDR), Extensively drug-resistant (XDR) and pan-drug resistant (PDR). Two hundred and ten bacterial isolates were from different sources (catheter tip, sputum, vaginal swab, urine, tracheal aspirate, blood, pus, nasal swab, stool, throat swab, pleural fluid, and ear swab). Isolates were identified based on their morphological characters and biochemical reaction. Antibiotics susceptibility screening was performed using twenty-three antibiotics from eighteen classes against all isolated Staphylococcus spp. following the Clinical and Laboratory Standards Institute (CLSI) guideline. The result revealed that out of 63 Gram-positive isolated bacteria, 52 (82.5%) were Staphylococcus spp. with a high incidence of S. aureus 37(71.2%). Out of all Staphylococcus spp., 38 (73.1%) were Methicillin-resistant (MR). The prevalence of MDR was higher in S. aureus (89.2%) than in S. epidermidis (75%). All Staphylococcus spp. displayed resistance to ampicillin and penicillin, while all S. aureus were sensitive to daptomycin and fosfomycin. One isolate was XDR possible PDR, while no PDR was reported in all isolated bacteria. This study provided evidence for the antimicrobial-resistant (AMR) burden in Sudan and highlighted the need for a practical and functional stewardship program to reduce the unreasonable costs of antibiotics.

Nanoparticles design considerations to co-deliver nucleic acids and anti-cancer drugs for chemoresistance reversal.

Chemoresistance and hence the consequent treatment failure is considerably challenging in clinical cancer therapeutics. The understanding of the genetic variations in chemoresistance acquisition encouraged the use of gene modulatory approaches to restore anti-cancer drug efficacy. Many smart nanoparticles are designed and optimized to mediate combinational therapy between nucleic acid and anti-cancer drugs. This review aims to define a rational design of such co-loaded nanocarriers with the aim of chemoresistance reversal at various cellular levels to improve the therapeutic outcome of anticancer treatment. Going through the principles of therapeutics loading, physicochemical characteristics tuning, and different nanocarrier modifications, also looking at combination effectiveness on chemosensitivity restoration. Up to now, these emerging nanocarriers are in development status but are expected to introduce outstanding outcomes.

Knowledge, attitude, and practice (KAP) regarding erectile dysfunction disease and its medications among community pharmacy technicians in Mogadishu Somalia.

Background: Erectile Dysfunction (ED) is the most common sexual dysfunction worldwide. This study is the first reported from Somalia to the best of our knowledge. Objective: The current study aimed to assess knowledge, attitude, and practice (KAP) regarding erectile dysfunction disease and its medications among community pharmacy technicians in Mogadishu, Somalia. Method: The current is a cross-sectional descriptive study conducted among pharmacy technicians in Mogadishu to assess their KAP regarding erectile dysfunction disease and its medications. A convenient sampling technique was used. A structured questionnaire contained 45 questions, including; demographic characteristics (4 items), the knowledge of erectile dysfunction disease and its medications (18 items), attitudes (5 items), and practice (15 items) were assessed among technicians. A total of 200 respondents participated in the study. Results: Knowledge. 79 and 72.5% of technicians comprehended the condition of ED and whom it affects; however, about half did not know the underlying risk factors and complications associated with PDE5 inhibitors. Attitude: 77-85% of technicians believe medication requires prescriptions, medications may have complications, and quality medications are essential. Practice: 64% of technicians give ED medication with prescriptions, and 85% do not consult a physician. 64.5% of technicians always provide the same type of medication, and 63% do not give the same dose to each client. About half of the technicians also vend herbal medicines to clients, such as honey, fish, and sea urchins. Conclusion: The findings of this study suggest pharmacy technicians have some knowledge, although not sufficient for understanding the risks and complications of medications. Technicians did not engage in good standard practices despite this knowledge and attitudes. These findings highlight the need for regulations to support good practice among pharmacy technicians and the quality, safety, and efficacy of medicines in Mogadishu by establishing the National Medicine Regulatory Authority.

Breakthrough daptomycin-, linezolid-, vancomycin-resistant Enterococcus faecium bacteremia during protracted daptomycin therapy: A case report.

Infections with multidrug resistant (MDR) Enterococcus faecium (Efm) are a growing problem. Vancomycin resistance in enterococci has long challenged treatment, necessitating the use of linezolid or daptomycin. Subsequently, daptomycin-, linezolid-, vancomycin-resistant Efm (DLVRE) infections have emerged. Case reports and guidelines for treating DLVRE infections are limited. Here, we describe the clinical and laboratory management of an MDR Efm protracted intraabdominal (IA) infection and breakthrough DLVRE bacteremia. Serial Efm resistance was evaluated using whole genome sequencing (WGS), susceptibility testing, and synergy analysis. Prior to in vitro synergy testing, combination antimicrobial therapy with daptomycin (DAP) and ceftaroline (CPT) was employed to treat the patient's central line-associated DLVRE bloodstream infection. In vitro antimicrobial testing revealed no synergy between daptomycin and ceftaroline; however, the patient's bacteremia cleared following initiation of both in conjunction with catheter removal. Sequencing of the DLVRE isolates revealed multiple genomic mutations which explained both linezolid and daptomycin resistance phenotypes and confirmed the presence of a plasmid containing the vanA operon. Sequential WGS of two additional bacterial isolates from the same patient revealed protracted colonization with a single DLVRE clone and suggested the development of bacterial subpopulations. Pairing clinical isolate susceptibilities with WGS and synergy testing should be encouraged in clinical practice to better inform antimicrobial management in cases of multidrug resistance.

Sphingosine-1-phosphate receptors 2 and 3 reprogram resting human macrophages into M1 phenotype following mycobacteria infection.

Mycobacteria tuberculosis (M.tb) the causative agent for tuberculosis has been accredited for a high rate of morbidity and mortality worldwide. The rise in MDR and XDR cases has further created new obstacles in achieving the "End TB Strategy", which is aimed for 2035. In this article, we have demonstrated the potential of sphingosine-1-phosphate (S1P) analogs in providing an anti-mycobacterial effector response by altering macrophage polarity into M1. Among S1PR1 and S1PR3 analogs, S1PR2 analogs proficiently favor selective polarization of infected human macrophages into M1 phenotypes, marked by increased expression of M1 markers and decreased M2 markers. Furthermore, S1PR1-3 analogs treated macrophages were also able to decrease the secretion of anti-inflammatory cytokine IL-10 and can induce NO secretion in infected macrophages. Lastly, only S1PR2-3 analogs were able to restrict the growth of mycobacteria in human macrophages. Taken together our study reflects the potential of S1PR2-3 analogs in providing host defenses following mycobacterial infection by favoring M1 macrophage polarization.

Diabetic foot ulcer in Southern Jordan: A cross-sectional Study of Clinical and Microbiological Aspects.

Background: Diabetes mellitus (DM) is a common metabolic disorder that significantly affects public health. Diabetic foot ulcer (DFU) is one of the serious complications of diabetes. DFU has a wide spectrum of bacterial isolates comprising Gram-positive, Gram-negative, aerobic bacteria and anaerobes. In the last two decades there has been an increase in the multidrug-resistant isolates (MDR). Materials and methods: This cross-sectional prospective observational study was conducted in southern Jordan among patients with DFU. The included variables are sociodemographic and clinical information. Isolates from swab culture of ulcers and antimicrobial susceptibility pattern are also recorded. Results: A total of 64 diabetic patients with DFU were included in this study. Most patients included in the study were males with male-to-female ratio of (2.2:1). The mean age was 54 years (SD ± 10.7). The mean duration of DM was 16.4 years (SD ± 7.5) and the mean HbA1c was 9.9% (SD ± 2.1). Neuropathy and anemia were noted in 72% and 44% of patients, respectively. The most frequent bacterial isolates were gram negative bacteria accounts for 29 isolates (45.3%). About 37.5% (24) of bacterial isolates showed MDR pattern. Previous antibiotic use in the last 30 days showed significant association with MDR bacteria (p-value <0.05). Previous history of amputations, presence of neuropathy, renal impairment, retinopathy, presence of anemia, limited joint mobility and presence of foot deformity were significantly associated with Wagner's grade ≥ three. Conclusion: Many factors affect and increase the risk of having high grade diabetic foot ulcer. The most frequent bacterial isolates from diabetic foot ulcers were gram negative bacteria. High rates of MDR in this study reflect the loose implementation of regulations in Jordan regarding antibiotics dispensing.

Prevalence of KPC-producing bacteria in negative gram of clinical samples obtained from patients.

Objective: Carbapenems are beta-lactam antibiotics that can play an important role in infections with multiple and severe resistance. The aim of this study was to investigate the frequency of carbapenem-producing bacteria in gram-negative isolates of clinical samples obtained from patients. Methods: 291 g-negative bacilli were isolated from the samples of hospitalized patients using gram staining method, conventional methods and biochemical tests. The antibiotic susceptibility of the isolates was determined using the agar disk diffusion method for 5 different antibiotics. Strains that were resistant to Meropenem antibiotic, KPC enzyme production was examined by the Modified Hodge test method. Results: Out of 291 g-negative bacilli, 14 isolates showed resistance to Meropenem by a disk agar diffusion method where 12 (85.8%) strains were producing KPC enzyme. The highest frequency of Gram-negative KPC-producing bacilli was related to Klebsiella pneumoniae and the most positive samples were urine. The prevalence of this type of bacteria was highest in NICU and the male internal ward, respectively. Conclusion: It was shown that carbapenem-resistant strains are considered as a growing problem in hospitals, especially in the intensive care unit for children and men.

Isolation and characterization of lytic bacteriophages from sewage at an egyptian tertiary care hospital against methicillin-resistant Staphylococcus aureus clinical isolates.

Background: Methicillin resistant Staphylococcus aureus (MRSA) is a pathogen to humans causing life-threatening infections. MRSA have the capability to grow resistance to many antibiotics, and phage therapy is one treatment option for this infection. Objectives: The aim of the present study was to isolate and characterize the lytic bacteriophages specific to MRSA from domestic sewage water at a tertiary care hospital in Egypt. Methods: Thirty MRSA strains were isolated from different clinical samples admitted to the microbiology lab at Theodor Bilharz Research institute (TBRI) hospital, Giza, Egypt. They were confirmed to be MRSA through phenotypic detection and conventional PCR for mecA gene. They were used for the isolation of phages from sewage water of TBRI hospital. Plaque assay was applied to purify and quantify the titer of the isolated phages. The host range of the isolated phages was detected using the spot test assay. The morphology of phages was confirmed using transmission electron microscope (TEM). Digestion of DNA extracted from phages with endonuclease enzymes including EcoRI and SmaI was performed. SDS-PAGE was performed to analyze MRSA specific phage proteins. As a positive control prophages were isolated from a mitomycin C (MitC) treated culture of S. aureus strain ATCC25923. Further characterization using conventional polymerase chain reaction (PCR) was used to select three known Staphylophages by detecting the endolysin gene of phage K, the polymerase gene of phage 44AHJD, and the minor tail gene of phage P68. Results: Isolated phages in this research displayed a wide host range against MRSA using the spot test, out of thirty tested MRSA isolates 24 were sensitive and got lysed (80%). The titer of the phages was estimated to be 1.04 × 106 pfu/ml using plaque test. Identification of head and tail morphology of the phages was achieved using TEM and they were designated to tailed phages of order Caudovirales, they composed an icosahedral capsid. Prophages were isolated through MitC induction. DNA of phages was digested by endonuclease enzymes. Conventional PCR yielded 341 bp of phage K endolysin gene and phage P68 minor tail protein gene 501 bp. Protein analysis using SDS-PAGE showed 4 proteins of sizes between 42 kDa and 140 kDa. Conclusion: Phages isolated here are alike to others mentioned in previous studies. The high broad host range of the isolated phages is promising to control MRSA and can be in the future commercially suitable for treatment as lysate preparations. Animal models of phage-bacterial interaction will be our next step that may help in resolving the multidrug resistant crisis of MRSA in Egypt.

Chest X-ray findings in drug-sensitive and drug-resistant pulmonary tuberculosis patients in Uganda.

Background: Tuberculosis (TB) is one of the leading causes of death worldwide. Radiology has an important role in the diagnosis of both drug-sensitive (DS) and rifampicin-resistant (RR) pulmonary TB (PTB). This study aimed to compare the chest x-ray (CXR) patterns of microbiologically confirmed DS and RR PTB cases stratified by HIV serostatus in Uganda. Methods: We conducted a hospital-based retrospective study at the Mulago National Referral Hospital (MNRH) TB wards. All participants had a microbiologically confirmed diagnosis of PTB. CXR findings extracted included infiltrates, consolidation, cavity, fibrosis, bronchiectasis, atelectasis, and other non-lung parenchymal findings. All films were examined by two independent radiologists blinded to the clinical diagnosis. Results: We analyzed CXR findings of 165 participants: 139 DS- and 26 RR-TB cases. The majority (n = 118, 71.7%) of the participants were seronegative for HIV. Overall, 5/165 (3%) participants had normal CXR. There was no statistically significant difference in the proportion of participants with consolidations (74.8% versus 88.5%; p = 0.203), bronchopneumonic opacities (56.1% versus 42.3%, p = 0.207) and cavities (38.1% versus 46.2%, p = 0.514), across drug susceptibility status (DS versus RR TB). Among HIV-infected participants, consolidations were predominantly in the middle lung zone in the DS TB group and in the lower lung zone in the RR TB group (42.5% versus 12.8%, p = 0.66). HIV-infected participants with RR TB had statistically significantly larger cavity sizes compared to their HIV uninfected counterparts with RR TB (7.7 ± 6.8 cm versus 4.2 ± 1.3 cm, p = 0.004). Conclusions: We observed that a vast majority of participants had similar CXR changes, irrespective of drug susceptibility status. However, HIV-infected RR PTB had larger cavities.The diagnostic utility of cavity sizes for the differentiation of HIV-infected and non-infected RR TB could be investigated further.

Tuberculosis: Past, present and future of the treatment and drug discovery research.

Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis. Despite decades of research driving advancements in drug development and discovery against TB, it still leads among the causes of deaths due to infectious diseases. We are yet to develop an effective treatment course or a vaccine that could help us eradicate TB. Some key issues being prolonged treatment courses, inadequate drug intake, and the high dropout rate of patients during the treatment course. Hence, we require drugs that could accelerate the elimination of bacteria, shortening the treatment duration. It is high time we evaluate the probable lacunas in research holding us back in coming up with a treatment regime and/or a vaccine that would help control TB spread. Years of dedicated and focused research provide us with a lead molecule that goes through several tests, trials, and modifications to transform into a 'drug'. The transformation from lead molecule to 'drug' is governed by several factors determining its success or failure. In the present review, we have discussed drugs that are part of the currently approved treatment regimen, their limitations, vaccine candidates under trials, and current issues in research that need to be addressed. While we are waiting for the path-breaking treatment for TB, these factors should be considered during the ongoing quest for novel yet effective anti-tubercular. If these issues are addressed, we could hope to develop a more effective treatment that would cure multi/extremely drug-resistant TB and help us meet the WHO's targets for controlling the global TB pandemic within the prescribed timeline.

Duration of carriage of multidrug-resistant bacteria in dogs and cats in veterinary care and co-carriage with their owners.

BACKGROUND: The emergence and spread of multidrug-resistant organisms (MDROs) represent a threat to human and animal health. OBJECTIVES: To assess duration of carriage of MDROs in dogs and cats presented to veterinary clinics/hospitals in Switzerland. To estimate prevalence, duration of and risk factors for MDRO carriage in their owners and the occurrence of co-carriage in owner-pet pairs. METHODS: Prospective, longitudinal, observational study. Nasal swabs and fecal samples were collected from 50 owners of dogs and cats presented to 3 large veterinary hospitals, 1 medium-sized clinic and 1 practice. If pet or owner tested positive for a MDRO, follow-up samples were collected for up to 8 months. Methicillin-resistant (MR) Staphylococcus aureus, MR S. pseudintermedius, MR coagulase-negative staphylococci (MRCoNS), MR Macrococcus spp., cephalosporinase- and carbapenemase-producing (CP) Enterobacterales were isolated and further characterized by MALDI-TOF MS, microdilution, ß-lactam resistance gene detection, REP/ERIC-PCR, multilocus sequence typing or whole-genome sequencing. Risk factors for MDRO carriage in owners were explored based on questionnaire-derived data. RESULTS: Five out of 50 owners carried 3rd generation cephalosporin-resistant Enterobacterales (3GC-R-Ent.), and 5/50 MRCoNS. In 3 dogs and 4 cats carriage of 3GC-R-Ent. persisted for up to 136 days after discharge (median 99 days, IQR 83 days, range 36-136 days), in two cats isolates were carbapenem-resistant. Owner-pet co-carriage was not observed. No specific risk factors for MDRO carriage in owners were identified. CONCLUSIONS: After discharge from veterinary care, dogs and cats may carry 3GC-R-Ent. for prolonged time periods. Carriage of MDROs was common in owners, but pet-owner co-carriage of the same MDRO was not observed.

The antibacterial activities of honey.

Honey is a powerful antimicrobial agent with a wide range of effects. Various components contribute to the antibacterial efficacy of honey: the sugar content; polyphenol compounds; hydrogen peroxide; 1,2-dicarbonyl compounds; and bee defensin-1. All of these elements are present at different concentrations depending on the source of nectar, bee type, and storage. These components work synergistically, allowing honey to be potent against a variety of microorganisms including multidrug resistant bacteria and modulate their resistance to antimicrobial agents. The effectiveness and potency of honey against microorganisms depends on the type of honey produced, which is contingent on its botanical origin, the health of the bee, its origin, and processing method. The application of antibiotics with honey yielded better antimicrobial potential and synergistic effects were noted against biofilms. In medicine, honey has been used in the treatment of surface wounds, burns, and inflammation, and has a synergistic effect when applied with antibiotics. Tissue repair is enhanced by the low pH of honey (3.5-4): causing a reduction in protease activity on the wound site, elevating oxygen release from hemoglobin and stimulating fibroblast and macrophage activity. Furthermore, H2O2 has antiseptic effects, and it disinfects the wound site and stimulates production of vascular endothelial growth factor. The use of honey will clean wounds or burn areas from free radicals and reduces scarring and contractures. The anti-inflammatory and antibacterial potential of honey will keep the injured area moist and as such prevents it from deterioration and fibrosis. Honey can promote fast healing and reduce scarring and is very convenient for plastic surgery. Skin maceration is protected by honey due to its high osmolarity and because it keeps the injury moist. In non-infected areas, honey still reduced pain and inflammation. In general, the use of honey in medical settings has reduced economic loss and provided proven economic benefits by lowering direct costs in comparison to conventional treatments and by using less antibiotics, faster healing and less hospitalization stay. This review is intended to provide an overview of the antibacterial activities of honey and its applications.

Bactericidal Properties of Rod-, Peanut-, and Star-Shaped Gold Nanoparticles Coated with Ceragenin CSA-131 against Multidrug-Resistant Bacterial Strains.

BACKGROUND: The ever-growing number of infections caused by multidrug-resistant (MDR) bacterial strains requires an increased effort to develop new antibiotics. Herein, we demonstrate that a new class of gold nanoparticles (Au NPs), defined by shape and conjugated with ceragenin CSA-131 (cationic steroid antimicrobial), display strong bactericidal activity against intractable superbugs. METHODS: For the purpose of research, we developed nanosystems with rod- (AuR NPs@CSA-131), peanut-(AuP NPs@CSA-131) and star-shaped (AuS NPs@CSA-131) metal cores. Those nanosystems were evaluated against bacterial strains representing various groups of MDR (multidrug-resistant) Gram-positive (MRSA, MRSE, and MLSb) and Gram-negative (ESBL, AmpC, and CR) pathogens. Assessment of MICs (minimum inhibitory concentrations)/MBCs (minimum bactericidal concentrations) and killing assays were performed as a measure of their antibacterial activity. In addition to a comprehensive analysis of bacterial responses involving the generation of ROS (reactive oxygen species), plasma membrane permeabilization and depolarization, as well as the release of protein content, were performed to investigate the molecular mechanisms of action of the nanosystems. Finally, their hemocompatibility was assessed by a hemolysis assay. RESULTS: All of the tested nanosystems exerted potent bactericidal activity in a manner resulting in the generation of ROS, followed by damage of the bacterial membranes and the leakage of intracellular content. Notably, the killing action occurred with all of the bacterial strains evaluated, including those known to be drug resistant, and at concentrations that did not impact the growth of host cells. CONCLUSIONS: Conjugation of CSA-131 with Au NPs by covalent bond between the COOH group from MHDA and NH3 from CSA-131 potentiates the antimicrobial activity of this ceragenin if compared to its action alone. Results validate the development of AuR NPs@CSA-131, AuP NPs@CSA-131, and AuS NPs@CSA-131 as potential novel nanoantibiotics that might effectively eradicate MDR bacteria.

Antibiotic resistance: Global health crisis and metagenomics.

Antibiotic resistance is a global problem which affects human health. The imprudent use of antibiotics (medicine, agriculture, aquaculture, and food industry) has resulted in the broader dissemination of resistance. Urban wastewater & sewage treatment plants act as the hotspot for the widespread of antimicrobial resistance. Natural environment also plays an important role in the dissemination of resistance. Mapping of antibiotic resistance genes (ARGS) in environment is essential for mitigating antimicrobial resistance (AMR) widespread. Therefore, the review article emphasizes on the application of metagenomics for the surveillance of antimicrobial resistance. Metagenomics is the next generation tool which is being used for cataloging the resistome of diverse environments. We summarize the different metagenomic tools that can be used for mining of ARGs and acquired AMR present in the metagenomic data. Also, we recommend application of targeted sequencing/ capture platform for mapping of resistome with higher specificity and selectivity.

Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice.

P-glycoprotein (P-gp), is an important efflux pump involved in chemotherapy resistance in human colon cancer. We investigated the efficacy of itraconazole as a P-gp inhibitor and its therapeutic synergistic relationship to paclitaxel through 99mTc-MIBI accumulation in HT-29 tumor-bearing nude mice. Histopathological screening along with in vitro experiments was done for further assessment. Itraconazole successfully inhibited P-gp mediated 99mTc-MIBI efflux, increasing its in vitro accumulation in itraconazole-receiving dishes. Notably, the co-administration of itraconazole with paclitaxel significantly enhanced the in vitro cytotoxicity effect of paclitaxel in itraconazole + paclitaxel wells containing HT-29 cells. Compared to the control, tumor volume in mice treated with itraconazole, paclitaxel and itraconazole +paclitaxel showed growth suppression approximately by 36.21, 60.02, and 73.3% respectively. And compared to paclitaxel group, the nude mice co-treated with paclitaxel and itraconazole showed suppression of tumor growth by about 33.31 % at the end of the treatment period. Also the biodistribution result showed that the co-administration of itraconazole with paclitaxel raised the mean tumor radioactivity accumulation compared to control and paclitaxel group. When given paclitaxel alone, the ID% of hepatic and cardiac tissue was reduced while co-administration of itraconazole with paclitaxel increased 99mTc-MIBI accumulation in these organs. Furthermore, the histopathological findings confirmed the biodistribution results. These results demonstrate that although monotherapy with itraconazole or paclitaxel has anti-tumor activity against HT-29 human colorectal cancer, a synergistic anti-tumor activity can be achieved when itraconazole is co-administered with paclitaxel. Also, 99mTc-MIBI is an effective radiotracer for monitoring response to treatment in MDR tumors.