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.

Epidemiological and microbiological characteristics of S. aureus pediatric infections in Colombia 2018-2021, a national multicenter study (Staphylored Colombia).

Background: Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of S. aureus in this patient group. Methods: We analyzed S. aureus isolates from WHONET-reporting centers. An "event" was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant S. aureus (MRSA) isolates. Results: Isolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 S. aureus culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (<0.001), with slightly higher rates observed in exclusively pediatric hospitals. In contrast, the MRSA rate was somewhat lower in centers with Antimicrobial Stewardship Program (ASP). MRSA was predominantly isolated from osteoarticular infections and multiple foci, while MSSA was more frequently associated with recurrent infections compared to MRSA. Conclusions: This is the largest study of pediatric S. aureus infections in Colombia. We found MSSA predominance, but resistance have important regional variations. S. aureus remains susceptible to other commonly used antibiotics such as TMP-SMX and clindamycin. Ongoing monitoring of S. aureus infections is vital for understanding their behavior in children. Prospective studies within the Staphylored LATAM are underway for a more comprehensive clinical and genetic characterization.

Isotretinoin self-nano-emulsifying drug delivery system: Preparation, optimization and antibacterial evaluation.

Purpose: Isotretinoin (ITN) is a poorly water-soluble drug. The objective of this study was to design a successful liquid self-nanoemulsifying drug delivery system (L-SNEDDS) for ITN to improve its solubility, dissolution rate, and antibacterial activity. Methods: According to solubility and emulsification studies, castor oil, Cremophor EL, and Transcutol HP were selected as system excipients. A pseudo ternary phase diagram was constructed to reveal the self-emulsification area. The developed SNEDDS were visually assessed, and the droplet size was measured. In vitro release studies and stability studies were conducted. The antimicrobial effectiveness against multiple bacterial strains, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and different accessory gene regulator (Agr) variants were investigated for the optimum ITN-loaded SNEDDS formulation. Results: Characterization studies showed emulsion homogeneity and stability (%T 95.40-99.20, A graded) with low droplet sizes (31.87 ± 1.23 nm-115.47 ± 0.36 nm). It was found that the developed ITN-SNEDDS provided significantly a higher release rate (>96 % in 1 h) as compared to the raw drug (<10 % in 1 h). The in vitro antimicrobial activities of pure ITN and ITN-loaded SNEDDS demonstrated a remarkable inhibitory effect on bacterial growth with statistically significant findings (p < 0.0001) for all tested strains when treated with ITN-SNEDDS as compared to the raw drug. Conclusion: These outcomes suggested that SNEDDS could be a potential approach for improving solubility, dissolution rates, and antibacterial activity of ITN.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain Positive for the Panton-Valentine Leucocidin Gene in a Middle-Aged Patient With Multiple Septic Pulmonary Emboli.

A 59-year-old man suffered from fever and chest pain for three days following an accidental bite to a lip ulcer. His lower lip showed swelling and tenderness, and chest computed tomography showed multiple bilateral nodules. He was diagnosed with septic pulmonary embolism and a lip abscess, and blood, sputum, and lip abscess cultures confirmed the presence of methicillin-resistant Staphylococcus aureus (MRSA). Despite the initiation of vancomycin, he rapidly developed respiratory failure and septic shock, necessitating intubation and noradrenaline support. Gentamicin was added on the seventh day of admission due to an insufficient effect, and vancomycin was switched to linezolid on the 14th day of admission. However, his respiratory failure persisted as bilateral pneumothorax developed. Blood culture was negative on the 14th day after admission, but the patient died on the 15th day after admission. The MRSA isolate was tested for the presence of the Panton-Valentine leukocidin (PVL) gene in conjunction with the USA300 strain. The prevalence of community-acquired (CA)-MRSA in the USA300 clone is increasing but still low in Japan, and this type of infection is commonly observed in people of all ages; this case is the first instance reported in Japan of a middle-aged patient with septic pulmonary embolism. Given the anticipated global increase in CA-MRSA infection caused by the USA300 clone and the emergence of USA300 with altered pathogenicity, it may be crucial to suspect PVL-positive CA-MRSA infections even in middle-aged or elderly patients presenting with septic pulmonary embolism as community infections.

COVID-19 and Cavitary Lesion in Lung.

The clinical manifestations of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are widespread, ranging from asymptomatic to critical illness with significant morbidity and mortality. It is widely known that individuals who have viral respiratory infections are more likely to develop bacterial infections. Throughout the pandemic, despite the fact that COVID-19 was thought to be the primary cause of millions of deaths, bacterial coinfections, superinfections, and other secondary complications played a significant role in the increased mortality rate. In our case, a 76-year-old male presented to the hospital complaining of shortness of air. Polymerase chain reaction (PCR) testing was positive for COVID-19 and cavitary lesions were discovered on imaging. Treatment was guided based on the results of bronchoscopy with bronchoalveolar lavage (BAL) cultures showing methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium gordonae. However, the case was later complicated by the development of a pulmonary embolism after anticoagulants were held due to new onset hemoptysis. Our case highlights the importance of considering bacterial coinfection in cavitary lung lesions, appropriate antimicrobial stewardship, and close follow-up for full recovery in COVID-19 infections.

Recent advances in engineered polymeric materials for efficient photodynamic inactivation of bacterial pathogens.

Nowadays, infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide. Especially bacterial infections remain a most severe concern due to the prevalence and emergence of multi-drug resistance (MDR) and limitations with existing therapeutic options. Antibacterial photodynamic therapy (APDT) is a potential therapeutic modality that involves the systematic administration of photosensitizers (PSs), light, and molecular oxygen (O2) for coping with bacterial infections. Although the existing porphyrin and non-porphyrin PSs were effective in APDT, the poor solubility, limited efficacy against Gram-negative bacteria, and non-specific distribution hinder their clinical applications. Accordingly, to promote the efficiency of conventional PSs, various polymer-driven modification and functionalization strategies have been adopted to engineer multifunctional hybrid phototherapeutics. This review assesses recent advancements and state-of-the-art research in polymer-PSs hybrid materials developed for APDT applications. Further, the key research findings of the following aspects are considered in-depth with constructive discussions: i) PSs-integrated/functionalized polymeric composites through various molecular interactions; ii) PSs-deposited coatings on different substrates and devices to eliminate healthcare-associated infections; and iii) PSs-embedded films, scaffolds, and hydrogels for regenerative medicine applications.

Clinical Presentation and Microbiological Profile of Deep Neck Space Infections in Different Age Groups.

Deep neck space infection (DNI), is defined as infections in the deep fascia enclosing potential spaces of the neck. In the past the diagnosis and treatment of DNI have challenged. The health care personnel at all levels. The complex anatomy and the deep location of this region remains a big problem with significant risks of morbidity and mortality. The aim of this study is to analyse the difference in clinical presentation and microbiology of DNI in different age groups. Eighty two patients with DNI which were managed at the Department of Otorhinolaryngology, ABVIMS and Dr. Ram Manohar Lohia Hospital New Delhi, between November 2017 and March 2019 formed the basis of our prospective cross sectional observational study. We observed that DNI is a frequent and potentially life threatening condition in children and adults despite the use of antibiotics. For appropriate surgical management knowledge of complex spaces of the neck and their communication with the other spaces is necessary.

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.

High-throughput sequencing technologies in the detection of livestock pathogens, diagnosis, and zoonotic surveillance.

Increasing globalization, agricultural intensification, urbanization, and climatic changes have resulted in a significant recent increase in emerging infectious zoonotic diseases. Zoonotic diseases are becoming more common, so innovative, effective, and integrative research is required to better understand their transmission, ecological implications, and dynamics at wildlife-human interfaces. High-throughput sequencing (HTS) methodologies have enormous potential for unraveling these contingencies and improving our understanding, but they are only now beginning to be realized in livestock research. This study investigates the current state of use of sequencing technologies in the detection of livestock pathogens such as bovine, dogs (Canis lupus familiaris), sheep (Ovis aries), pigs (Sus scrofa), horses (Equus caballus), chicken (Gallus gallus domesticus), and ducks (Anatidae) as well as how it can improve the monitoring and detection of zoonotic infections. We also described several high-throughput sequencing approaches for improved detection of known, unknown, and emerging infectious agents, resulting in better infectious disease diagnosis, as well as surveillance of zoonotic infectious diseases. In the coming years, the continued advancement of sequencing technologies will improve livestock research and hasten the development of various new genomic and technological studies on farm animals.

Two-stage skin grafting using a basic fibroblast growth factor-impregnated artificial dermis.

For traditional artificial dermises, a waiting period of approximately three weeks is required after the first implantation before they are adequately vascularized. The objective of this retrospective case series was to investigate whether full-thickness skin defects, requiring surgical reconstruction, could be successfully treated by implantation of a basic fibroblast growth factor (bFGF)-impregnated artificial dermis and secondary skin grafting with a shorter waiting period. Between January 2019 and January 2021, 19 skin defects in 14 patients (7 male and 7 female) were treated with two-stage skin grafting using bFGF-impregnated collagen-gelatin sponge (CGS). All of them were included in this case series, and the waiting period for skin grafting, success rate of skin grafting, infection during the waiting period, and scar quality 6-12 months postoperatively were retrospectively investigated. As a result, all skin grafting surgeries were successfully performed with a waiting period of 13.3 ± 4.3 days. Infection during the waiting period was observed in three lesions (15.8%); however, all infections were controllable. Postoperative scar quality was acceptable (Vancouver Scar Scale score range, 1-8). In conclusion, compared to traditional artificial dermises, bFGF-impregnated CGSs have the potential to shorten the waiting period without decreasing the success rate of skin grafting. Further studies are required to confirm this finding.

Roles and current applications of S-nitrosoglutathione in anti-infective biomaterials.

Bacterial infections can compromise the physical and biological functionalities of humans and pose a huge economical and psychological burden on infected patients. Nitric oxide (NO) is a broad-spectrum antimicrobial agent, whose mechanism of action is not affected by bacterial resistance. S-nitrosoglutathione (GSNO), an endogenous donor and carrier of NO, has gained increasing attention because of its potent antibacterial activity and efficient biocompatibility. Significant breakthroughs have been made in the application of GSNO in biomaterials. This review is based on the existing evidence that comprehensively summarizes the progress of antimicrobial GSNO applications focusing on their anti-infective performance, underlying antibacterial mechanisms, and application in anti-infective biomaterials. We provide an accurate overview of the roles and applications of GSNO in antibacterial biomaterials and shed new light on the avenues for future studies.

Molecular phenotyping approaches for the detection and monitoring of carbapenem-resistant Enterobacteriaceae by mass spectrometry.

Antimicrobial resistance is increasing in prevalence and there is a clear need for the development of rapid detection methods in clinical diagnostics. This review explores -omics studies utilising mass spectrometry to investigate the molecular phenotype associated with carbapenem resistance. Whilst the specific mechanisms of carbapenem resistance are well characterised, the resistant phenotype is poorly understood. Understanding how the acquisition of resistance affects cellular physiology and cell metabolism through molecular phenotyping is a necessary step towards detecting resistance by diagnostic means. In addition, this article examines the potential of mass spectrometry for the identification of resistance biomarkers through molecular profiling of bacteria. Developments in mass spectrometry platforms are expanding the biomarker-based diagnostic landscape. Targeted measures, such as high-resolution mass spectrometry coupled with chromatographic separation show considerable promise for the identification of molecular signatures and the development of a rapid diagnostic assay for the detection of carbapenem resistance.

Fulminant infectious endocarditis caused by Staphylococcus aureus with pseudoaneurysms in the superior mesenteric, hepatic, and popliteal arteries: a case report.

Staphylococcus aureus infectious endocarditis has a high mortality, major causes of death being cardiac failure, systemic embolism, and sepsis. Pseudoaneurysms, a rare complication of this infection, are not invariably fatal with appropriate treatment. A previously healthy 32-year-old man was found to have multiple cerebral infarctions, and infectious endocarditis with mitral valve vegetation was diagnosed by echocardiography. Because methicillin-resistant Staphylococcus aureus (MRSA) was identified from blood cultures, vancomycin was administered. Massive intracerebral hemorrhage in the left temporo-occipital lobe occurred in the patient on the 3rd day after admission, and the hematoma was completely removed surgically. Another hemorrhage was identified in the right occipital region on the 7th hospital day, which led the patient deep coma. Blood cultures on the 10th day were negative for MRSA; however, imaging studies revealed pseudoaneurysms in the superior mesenteric, hepatic, and left popliteal arteries 3 weeks after admission. No surgical indication was applied to these pseudoaneurysms because the patient remained comatose. On the 78th day after admission, the patient's blood pressure suddenly dropped and he died. Autopsy demonstrated massive bleeding in the abdominal cavity caused by rupture of the superior mesenteric artery pseudoaneurysm. Our patient's clinical course was fulminant, his endocarditis being complicated by cerebral infarctions, intracranial hemorrhages, and multiple pseudoaneurysms within 3 weeks of admission. In retrospect, he may have survived if emergency resection of the mitral valve vegetation had been performed on the first or second day of admission; however, the in-hospital mortality rate after such surgery is high.

Usefulness of molecular typing methods for epidemiological and evolutionary studies of Staphylococcus aureus isolated from bovine intramammary infections.

In cattle, Staphylococcus aureus is a major pathogen of increasing importance due to its association with intramammary infections (IMIs), which are a primary cause of antibiotic use on farms and thus of the rise in antibiotic resistance. Methicillin-resistant S. aureus (MRSA), which are frequently isolated from cases of bovine mastitis, represent a public health problem worldwide. Understanding the epidemiology and the evolution of these strains relies on typing methods. Such methods were phenotypic at first, but more recently, molecular methods have been increasingly utilized. Multiple-locus variable number tandem repeat analysis (MLVA), a high-throughput molecular method for determining genetic diversity and the emergence of host- or udder-adapted clones, appears to be the most useful PCR-based method. Despite the difficulties present in reproducibility, interlaboratory reliability, and hard work, it is agreed that pulsed-field gel electrophoresis (PFGE) remains the gold standard, particularly for short-term surveillance. Multilocus sequence typing (MLST) is a good typing method for long-term and global epidemiological investigations, but it is not suitable for outbreak investigations. Staphylococcal protein A (spa) typing is the most widely used method today for first-line typing in the study of molecular evolution, and outbreaks investigations. Staphylococcal cassette chromosome mec (SCCmec) typing has gained popularity for the evolutionary analysis of MRSA strains. Whole-genome sequencing (WGS) and DNA microarrays that represent relatively new DNA-based technologies, provide more information for tracking antibioresistant and virulent outbreak strains. They offer a higher discriminatory power, but are not suitable for routine use in clinical veterinary medicine at this time. Descriptions of the evolution of these methods, their advantages, and limitations are given in this review.

Comparison of three culture media in assessing the sensitivity of antibiotics to common foodborne microorganisms.

This study aimed to determine the antibiotic susceptibility of seven antibiotics, (Amoxicillin (AX), Ampicillin (AM), Chloramphenicol (C), Ciprofloxacin (CIP), Doxycycline (DO), Gentamicin (CN) and Neomycin (N)) on some common microorganisms that cause food poisoning. Furthermore, we aimed to compare three types of culture media in assessing antibiotics susceptibility. A sensitivity test was carried out using six bacterial isolates: Micrococcus spp., Staphylococcus aureus, Escherichia coli, Salmonella spp., Proteus mirabilis, Pseudomonas aeruginosa. These bacterial isolates were identified at the Food Microbiology Division, Public Health Laboratory using three culture media: Mueller Hinton Agar (MHA), Antibiotic Assay Medium A (AAM), and nutrient agar (NA). The results showed that all of these media are suitable to test antibiotic sensitivity. Bacterial sensitivity and resistance between these media (P≤0.01) were recorded, with significant differences found at the tested probability level.

Case Series of Percutaneous Mechanical Aspiration of Mitral Valve Endocarditis.

Infective endocarditis of the mitral valve that is refractory to medical therapy requires surgical debridement. However, patients who are high risk for surgery have limited options. We report 3 cases of refractory infective endocarditis involving the mitral valve that were treated with percutaneous mechanical aspiration with an embolic protection system. (Level of Difficulty: Intermediate.).

Evolving and assembling to pierce through: Evolutionary and structural aspects of antimicrobial peptides.

The burgeoning menace of antimicrobial resistance across the globe has necessitated investigations into other chemotherapeutic strategies to combat infections. Antimicrobial peptides, or host defense peptides, are a set of promising therapeutic candidates in this regard. Most of them cause membrane permeabilization and are a key component of the innate immune response to pathogenic invasion. It has also been reported that peptide self-assembly is a driving factor governing the microbicidal activity of these peptide candidates. While efforts have been made to develop novel synthetic peptides against various microbes, many clinical trials of such peptides have failed due to toxicity and hemolytic activity to the host. A function-guided rational peptide engineering, based on evolutionary principles, physicochemical properties and activity determinants of AMP activity, is expected to help in targeting specific microbes. Furthermore, it is important to develop a unified understanding of the evolution of AMPs in order to fully appreciate their importance in host defense. This review seeks to explore the evolution of AMPs and the physicochemical determinants of AMP activity. The specific interactions driving AMP self-assembly have also been reviewed, emphasizing implications of this self-assembly on microbicidal and immunomodulatory activity.

Multi-site implementation of whole genome sequencing for hospital infection control: A prospective genomic epidemiological analysis.

Background: Current microbiological methods lack the resolution to accurately identify multidrug-resistant organism (MDRO) transmission, however, whole genome sequencing can identify highly-related patient isolates providing opportunities for precision infection control interventions. We investigated the feasibility and potential impact of a prospective multi-centre genomics workflow for hospital infection control. Methods: We conducted a prospective genomics implementation study across eight Australian hospitals over 15 months (2017,2018), collecting all clinical and screening isolates from inpatients with vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec), or ESBL Klebsiella pneumoniae (ESBL-Kp). Genomic and epidemiologic data were integrated to assess MDRO transmission. Findings: In total, 2275 isolates were included from 1970 patients, predominantly ESBL-Ec (40·8%) followed by MRSA (35·6%), vanA VRE (15·2%), and ESBL-Kp (8·3%).Overall, hospital and genomic epidemiology showed 607 patients (30·8%) acquired their MDRO in hospital, including the majority of vanA VRE (266 patients, 86·4%), with lower proportions of ESBL-Ec (186 patients, 23·0%), ESBL-Kp (42 patients, 26·3%), and MRSA (113 patients, 16·3%). Complex patient movements meant the majority of MDRO transmissions would remain undetected without genomic data.The genomics implementation had major impacts, identifying unexpected MDRO transmissions prompting new infection control interventions, and contributing to vanA VRE becoming a notifiable condition. We identified barriers to implementation and recommend strategies for mitigation. Interpretation: Implementation of a multi-centre genomics-informed infection control workflow is feasible and identifies many unrecognised MDRO transmissions. This provides critical opportunities for interventions to improve patient safety in hospitals. Funding: Melbourne Genomics Health Alliance (supported by State Government of Victoria, Australia), and National Health and Medical Research Council (Australia).