Worldwide Antimicrobial Resistance Research Articles

One-Pot Synthesis of Silver/Zirconium Nanoparticles Using Sargassum tenerrimum for the Evaluation of Their Antibacterial and Antioxidant Activities.

The global health threat posed by worldwide antimicrobial resistance necessitated immediate multisectoral action by the scientific community to achieve sustainable development goals. Silver and zirconium nanoparticles (Ag/ZrO-NPs), known for their antimicrobial properties, have the potential to combat pathogens effectively, making them versatile for various applications across different fields. This study aims to synthesize and characterize Sargassum tenerimum-mediated Ag/ZrO-NPs and evaluate their antioxidant and antibacterial efficacy against multidrug resistant (MDR) pathogens. The synthesis of Ag/ZrO-NPs using the one-pot green synthesis method was conducted and followed by using characterization techniques, namely, UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), X-ray diffraction analysis (XRD), and energy-dispersive X-ray analysis (EDX). The antibacterial activity was assessed using the agar well diffusion method, and antioxidant activity was determined using the DPPH(2,2-diphenyl-1-picrylhydrazyl) method. Statistical analysis was analyzed using the IBM SPSS Statistics for Windows, version 21.0 (released 2012, IBM Corp., Armonk, NY). The green-synthesized Ag/ZrO-NPs exhibited acolor change from dark brown to creamy white, indicating the successful reduction of the nanoparticles. UV-analysis peaks were observed at 310-330 nm, while the FT-IRanalysis showed the peaks at various wavelengths, such as 648.9 cm-1 (alkyne C-H bond), 1041.14 cm-1 (aliphatic fluoro compounds, C-F stretch), 1382.54 cm-1 (dimethyl -CH3), 1589.6 cm-1 (primary amine, N-H bond), and 3353.8 cm-1 (aliphatic secondary amine, N-H stretch). The crystallinity of the nanoparticles was determined to be 59.5%, while the remaining 40.5% exhibited an amorphous structure.The SEM image revealed the spherically agglomeratedstructure of the nano-ranged size Ag/ZrO-NPs. The EDX analysis indicated the presence of elemental compositions Zr (16.2%), Ag (18.8%), and C (28.7%)in the green-synthesized Ag/ZrO-NPs. These nanoparticles demonstrated significant antibacterial activity against Pseudomonas aeruginosa, Enterococcus faecalis, and Methicillin-resistant Staphylococcus aureus (MRSA). The moderate antibacterial activity against E. coli showed thesignificant antioxidant activity in a dose-dependent manner. The green-synthesized Ag/ZrO-NPs showed notable antibacterial and antioxidant activity. In future aspects, it may be used as a potential drug after completion of in-vivo and in-vitro studies.

Chemical Nose Strategy with Metabolic Labeling and "Antibiotic-Responsive Spectrum" Enables Accurate and Rapid Pathogen Identification.

The worldwide antimicrobial resistance (AMR) dilemma urgently requires rapid and accurate pathogen phenotype discrimination and antibiotic resistance identification. The conventional protocols are either time-consuming or depend on expensive instrumentations. Herein, we demonstrate a metabolic-labeling-assisted chemical nose strategy for phenotyping classification and antibiotic resistance identification of pathogens based on the "antibiotic-responsive spectrum" of different pathogens. d-Amino acids with click handles were metabolically incorporated into the cell wall of pathogens for further clicking with dibenzocyclooctyne-functionalized upconversion nanoparticles (DBCO-UCNPs) in the presence/absence of six types of antibiotics, which generates seven-channel sensing responses. With the assistance of machine learning algorithms, eight types of pathogens, including three types of antibiotic-resistant bacteria, can be well classified and discriminated in terms of microbial taxonomies, Gram phenotypes, and antibiotic resistance. The present metabolic-labeling-assisted strategy exhibits good anti-interference capability and improved discrimination ability rooted in the unique sensing mechanism. Sensitive identification of pathogens with 100% accuracy from artificial urinary tract infection samples at a concentration as low as 105 CFU/mL was achieved. Pathogens outside of the training set can also be discriminated well. This clearly demonstrated the potential of the present strategy in the identification of unknown pathogens in clinical samples.

Producing Tailocins from Phages Using Osmotic Shock and Benzalkonium Chloride.

In the light of the worldwide antimicrobial resistance crisis, new substitutes to antibiotics are urgently needed. Tailocins or phage tail-like bacteriocin particles, produced by bacteria for environmental competition, are a potential antimicrobial alternative to antibiotic treatment. Yet, the availability of characterized Tailocins is limited. We explored the possibility to produce new Tailocins from phage particles, using osmotic shock or chemical treatment by the ammonium quaternary compound benzalkonium chloride on Ackermannviridae phage S117 and using Straboviridae phage T4 as control. We report that phage S117 was resistant to such treatment, while successful production of Tailocins by osmotic shock was achieved for phage T4. Finally, chemical treatment with benzalkonium chloride was inefficient on phage S117 but successfully inactivated phage T4 without production of Tailocins. Further studies are needed to implement such treatments of phages for producing Tailocins with killing activity.

Polyglycerol Adipate-Grafted Polycaprolactone Nanoparticles as Carriers for the Antimicrobial Compound Usnic Acid.

Nanoparticle (NP) drug delivery systems are known to potentially enhance the efficacy of therapeutic agents. As for antimicrobial drugs, therapeutic solutions against drug-resistant microbes are urgently needed due to the worldwide antimicrobial resistance issue. Usnic acid is a widely investigated antimicrobial agent suffering from poor water solubility. In this study, polymer nanoparticles based on polyglycerol adipate (PGA) grafted with polycaprolactone (PCL) were developed as carriers for usnic acid. We demonstrated the potential of the developed systems in ensuring prolonged bactericidal activity against a model bacterial species, Staphylococcus epidermidis. The macromolecular architecture changes produced by PCL grafted from PGA significantly influenced the drug release profile and mechanism. Specifically, by varying the length of PCL arms linked to the PGA backbone, it was possible to tune the drug release from a burst anomalous drug release (high PCL chain length) to a slow diffusion-controlled release (low PCL chain length). The developed nanosystems showed a prolonged antimicrobial activity (up to at least 7 days) which could be used in preventing/treating infections occurring at different body sites, including medical device-related infection and mucosal/skin surface, where Gram-positive bacteria are commonly involved.

Discovery and Characterization of Synthesized and FDA-Approved Inhibitors of Clostridial and Bacillary Collagenases.

In view of the worldwide antimicrobial resistance (AMR) threat, new bacterial targets and anti-infective agents are needed. Since important roles in bacterial pathogenesis have been demonstrated for the collagenase H and G (ColH and ColG) from Clostridium histolyticum, collagenase Q1 and A (ColQ1 and ColA) from Bacillus cereus represent attractive antivirulence targets. Furthermore, repurposing FDA-approved drugs may assist to tackle the AMR crisis and was addressed in this work. Here, we report on the discovery of two potent and chemically stable bacterial collagenase inhibitors: synthesized and FDA-approved diphosphonates and hydroxamates. Both classes showed high in vitro activity against the clostridial and bacillary collagenases. The potent diphosphonates reduced B. cereus-mediated detachment and death of cells and Galleria mellonella larvae. The hydroxamates were also tested in a similar manner; they did not have an effect in infection models. This might be due to their fast binding kinetics to bacterial collagenases.

In Vitro Genotoxicity Evaluation of an Antiseptic Formulation Containing Kaolin and Silver Nanoparticles

Worldwide antimicrobial resistance is partly caused by the overuse of antibiotics as growth promoters. Based on the known bactericidal effect of silver, a new material containing silver in a clay base was developed to be used as feed additive. An in vitro genotoxicity evaluation of this silver-kaolin clay formulation was conducted, which included the mouse lymphoma assay in L5178Y TK+/− cells and the micronucleus test in TK6 cells, following the principles of the OECD guidelines 490 and 487, respectively. As a complement, the standard and Fpg-modified comet assays for the evaluation of strand breaks, alkali labile sites and oxidative DNA damage were also performed in TK6 cells. The formulation was tested without metabolic activation after an exposure of 3 h and 24 h; its corresponding release in medium, after the continuous agitation of the silver-kaolin for 24 h was also evaluated. Under the conditions tested, the test compound did not produce gene mutations, chromosomal aberrations or DNA damage (i.e., strand breaks, alkali labile sites or oxidized bases). Considering the results obtained in the present study, the formulation seems to be a promising material to be used as antimicrobial in animal feed.

Clinical Perspective of Antimicrobial Resistance in Bacteria.

Antimicrobial resistance (AMR) has become a global clinical problem in recent years. With the discovery of antibiotics, infections were not a deadly problem for clinicians as they used to be. However, worldwide AMR comes with the overuse/misuse of antibiotics and the spread of resistance is deteriorated by a multitude of mobile genetic elements and relevant resistant genes. This review provides an overview of the current situation, mechanism, epidemiology, detection methods and clinical treatment for antimicrobial resistant genes in clinical important bacteria including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), penicillin-resistant Streptococcus pneumoniae (PRSP), extended-spectrum β-lactamase-producing Enterobacteriaceae, acquired AmpC β-lactamase-producing Enterobacteriaceae, carbapenemase-producing Enterobacteriaceae (CPE), multidrug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa.

Treatment of Impetigo and Antimicrobial Resistance.

Impetigo is a contagious bacterial infection that affects the superficial skin layers. Increasing worldwide antimicrobial resistance (AMR) to existing topical agents commonly prescribed to treat impetigo is central to treatment failure. The Worldwide Health Organization developed a global action plan on AMR, but omitted information about AMR stewardship programs for topical antibiotics. The review aims to provide information to clinicians and stakeholders regarding AMR and antimicrobial stewardship on topical antimicrobial drugs for impetigo treatment. The literature searches reviewed the status of AMR to current topical antibiotics in impetigo, current therapeutic behavior, and concordance with antimicrobial stewardship principles. Two international panels convened to discuss the output of the searches, and the results of the panel discussions were used in the development of the manuscript. The literature search included clinical trials, research studies, clinical guidelines, consensus papers, and reviews (if they provided original data), published between January 2008 and May 2019. The articles were selected based on clinical relevancy of impetigo management, clinical efficacy, and safety of the treatment and antimicrobial resistance. The searches resulted in one-hundred and ninety-eight articles. After applying the eligibility criteria, nineteen articles met inclusion criteria and were considered in the present review. While published antimicrobial stewardship guidelines have focused on systemic antibiotics, few studies have attempted to evaluate topical antibiotic prescribing practices for impetigo treatment. Many of the topical impetigo treatments currently in use have developed resistance. The appropriate use of topical ozenoxacin can help eradicate impetigo while minimizing AMR.J Drugs Dermatol. 20(4):366-372. doi:10.36849/JDD.5795.

Treatment of Impetigo and Antimicrobial Resistance

Background: Impetigo is a contagious bacterial infection that affects the superficial skin layers. Increasing worldwide antimicrobial resistance (AMR) to existing topical agents commonly prescribed to treat impetigo is central to treatment failure. The Worldwide Health Organization developed a global action plan on AMR, but omitted information about AMR stewardship programs for topical antibiotics. Objectives: The review aims to provide information to clinicians and stakeholders regarding AMR and antimicrobial stewardship on topical antimicrobial drugs for impetigo treatment. Methods: The literature searches reviewed the status of AMR to current topical antibiotics in impetigo, current therapeutic behavior, and concordance with antimicrobial stewardship principles. Two international panels convened to discuss the output of the searches, and the results of the panel discussions were used in the development of the manuscript. Results: The literature search included clinical trials, research studies, clinical guidelines, consensus papers, and reviews (if they provided original data), published between January 2008 and May 2019. The articles were selected based on clinical relevancy of impetigo management, clinical efficacy, and safety of the treatment and antimicrobial resistance. The searches resulted in one-hundred and ninety-eight articles. After applying the eligibility criteria, nineteen articles met inclusion criteria and were considered in the present review. Conclusions: While published antimicrobial stewardship guidelines have focused on systemic antibiotics, few studies have attempted to evaluate topical antibiotic prescribing practices for impetigo treatment. Many of the topical impetigo treatments currently in use have developed resistance. The appropriate use of topical ozenoxacin can help eradicate impetigo while minimizing AMR.J Drugs Dermatol. 20(4):366-372. doi:10.36849/JDD.5795

Molecular Characteristics of Extraintestinal Pathogenic E. coli (ExPEC), Uropathogenic E. coli (UPEC), and Multidrug Resistant E. coli Isolated from Healthy Dogs in Spain. Whole Genome Sequencing of Canine ST372 Isolates and Comparison with Human Isolates Causing Extraintestinal Infections.

Under a one health perspective and the worldwide antimicrobial resistance concern, we investigated extraintestinal pathogenic Escherichia coli (ExPEC), uropathogenic E. coli (UPEC), and multidrug resistant (MDR) E. coli from 197 isolates recovered from healthy dogs in Spain between 2013 and 2017. A total of 91 (46.2%) isolates were molecularly classified as ExPEC and/or UPEC, including 50 clones, among which (i) four clones were dominant (B2-CH14-180-ST127, B2-CH52-14-ST141, B2-CH103-9-ST372 and F-CH4-58-ST648) and (ii) 15 had been identified among isolates causing extraintestinal infections in Spanish and French humans in 2015 and 2016. A total of 28 (14.2%) isolates were classified as MDR, associated with B1, D, and E phylogroups, and included 24 clones, of which eight had also been identified among the human clinical isolates. We selected 23 ST372 strains, 21 from healthy dogs, and two from human clinical isolates for whole genome sequencing and built an SNP-tree with these 23 genomes and 174 genomes (128 from canine strains and 46 from human strains) obtained from public databases. These 197 genomes were segregated into six clusters. Cluster 1 comprised 74.6% of the strain genomes, mostly composed of canine strain genomes (p < 0.00001). Clusters 4 and 6 also included canine strain genomes, while clusters 2, 3, and 5 were significantly associated with human strain genomes. Finding several common clones and clone-related serotypes in dogs and humans suggests a potentially bidirectional clone transfer that argues for the one health perspective.

Exploring barriers to and enablers of antimicrobial stewardship in rural health services.

World-wide antimicrobial resistance is increasing, and antimicrobial stewardship (AMS) interventions aimed at increasing compliance with optimal antimicrobial prescribing are essential in tackling this issue. Local level research about antimicrobial use is important to tailor interventions in a place-based approach to solve local level problems. As part of a broader mixed methods study, Medical Practitioners and Senior Nurses at three rural health services were invited by email to participate in interviews to explore opinions and practices of antimicrobial prescribing. Seven Medical Practitioners and thirteen Senior Nurses from three small rural health services participated in the study. The major findings were that nurses were perceived as the 'gatekeepers' to antimicrobial initiatives by all participants. Senior Nurses perceived AMS activities as being a link in a world-wide program to eradicate antimicrobial resistance, while Medical Practitioners perceived it as a local level program, aimed at educating individual prescribers. There was consensus that an intervention aimed at improved documentation at the point of prescribing and increased accessibility to antimicrobial prescribing guidelines had a high potential for increased compliance with optimal prescribing of antimicrobials. The research enabled identification of interventions aimed at increasing optimal compliance with antimicrobial prescribing that are acceptable to and appropriate for Medical Practitioners and nursing staff at three rural health services.

KNOWLEDGE Of ANTIBIOTIC USE, MISUSE AND ANTIBIOTIC RESISTANCE IN THE SLUM COMMUNITY IN KARACHI

Background: Worldwide antimicrobial resistance is hugely increasing in the response of inappropriate antibiotic use. Our objectives were to assess knowledge of antibiotic use, misuse and antibiotic resistance in the slum community of Karachi. Methods: This Community-based cross-sectional study was carried out Shireen Jinnah Colony in Karachi for the period of six months from 1st January to 30th June 2017.Subjects of both genders were approached through convenient non-probability sampling technique. Subjects of both genders having age 15 years and above and who were willing to participate in the study were included. An adapted and validated questionnaire was used for data collection. Results: Out of total 120 subjects, the majority of 100 (83.3%) were males, 64 (53.3%) married, 36 (30%) were matriculate and 54.2% fell in the age group between 15-30 years of age. Majority of 77.5% participants never attended any seminar or workshop about antibiotic resistance. Most of 73.33% subjects answered that antibiotics are effective in treating both bacterial and viral infections. 60.83% of respondents purchase antibiotic with the prescription. 70 % of subjects knew about antibiotic adverse drug reaction. In addition, 60.83% stop the antibiotic medication when feeling better. Conclusion: The study concluded the lack of knowledge of the use of antibiotics and the unnecessary and improper use of the antibiotic may cause antibiotic resistance.

Activity of ceftaroline against pathogens associated with community-acquired pneumonia collected as part of the AWARE surveillance program, 2015–2016

We report Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) program data for ceftaroline and comparators against isolates collected from identified lower respiratory tract sources in 2015 and 2016. MICs and susceptibility were determined using CLSI broth microdilution methodology and EUCAST breakpoints. Ceftaroline susceptibility among penicillin-resistant Streptococcus pneumoniae (MIC≥4 mg/L [nonmeningitis breakpoint]) ranged from 77.4% (Asia, 72/93) to 100% (Oceania, 16/16; Latin America, 15/15). Among MRSA, ceftaroline susceptibility ranged from 72.3% (Asia, 553/765) to 100% (Oceania, 39/39). Among β-lactamase–positive Haemophilus influenzae, ceftaroline susceptibility ranged from 69.2% (Asia, 36/52) to 100% (Oceania, 19/19). Susceptibility to ceftaroline against non–ESBL-producing Klebsiella pneumoniae was between 91.4% (Europe, 659/721) and 100% (Oceania, 55/55) and for Escherichia coli between 85.7% (Africa/Middle East, 42/49) and 92.1% (Oceania, 35/38). Ceftaroline is not active against ESBL producers. In this study, susceptibility to ceftaroline was high among the S. pneumoniae, Staphylococcus aureus, β-lactamase–negative H. influenzae, and ESBL-negative K. pneumoniae and E. coli collected.

Ciprofloxacin resistance in uropathogenic Escherichia coli isolates causing community-acquired urinary infections in Brasília, Brazil

Considering the global concern of ciprofloxacin resistance, the aim of this study was to evaluate the characteristics of ciprofloxacin-resistant (CIP-R) Escherichia coli isolated from patients with community-acquired urinary tract infections (UTIs) in Brasília, Brazil. CIP-R E. coli isolated from different outpatients between July 2013 and April 2014 in a tertiary hospital were analysed for antibiotic resistance profile, phylotype, uropathogenic E. coli (UPEC) virulence genes, clonal relationship by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR), and multilocus sequence typing (MLST). Among the 324 UPEC analysed, 263 (81.2%) were ciprofloxacin-sensitive and 61 (18.8%) were CIP-R. Antibiogram analysis of the 61 CIP-R strains showed that 45 (73.8%) were also multidrug-resistant. The most prevalent phylogroups were A and B2 (26/61 and 18/61, respectively). traT (53/61) and aer-traT (24/61) were the most common gene and genotype observed. Dendrogram analysis found that multidrug resistance and virulence genes were distributed among CIP-R strains independently of clonality and phylogroup. Six ERIC clusters (strains sharing ≥85% genetic similarity) were observed. MLST analysis of all strains of each cluster identified sequence types (STs) associated with worldwide antimicrobial resistance dissemination, including B2-ST131 and ST410, as well as STs not yet associated with antimicrobial resistance propagation, such as ST1725 and ST179. These results demonstrate that ciprofloxacin resistance dissemination by UPEC causing community-acquired UTIs was associated with multidrug resistance and was promoted by pandemic and non-pandemic STs, a concerning scenario for the local population.

In vitro activity of Ceftaroline against bacterial pathogens isolated from patients with skin and soft tissue and respiratory tract infections in African and Middle Eastern countries: AWARE global surveillance program 2012–2014

The objective of this report was to document antimicrobial susceptibility testing surveillance data for ceftaroline and comparative agents from the AWARE (Assessing Worldwide Antimicrobial Resistance Evaluation) global surveillance program for bacterial pathogens causing skin and soft tissue and respiratory tract infections in African and Middle Eastern countries from 2012 through 2014. Pathogen identities were confirmed by MALDI-TOF and antimicrobial susceptibility testing performed by CLSI broth microdilution methodology in a central laboratory. All methicillin-susceptible Staphylococcus aureus (MSSA) (n= 923; MIC90, 0.25 μg/mL) and 91.8% of methicillin-resistant S. aureus (MRSA) (n= 1161; MIC90, 1 μg/mL) tested were susceptible to ceftaroline. The maximum ceftaroline MIC observed for isolates of MRSA was 2 μg/mL. All Streptococcus pyogenes (n= 174; MIC90, 0.008 μg/mL), Streptococcus agalactiae (n= 44; MIC90, 0.015 μg/mL), Streptococcus pneumoniae (n= 351; MIC90, 0.25 μg/mL), and Haemophilus influenzae (n= 84; MIC90, ≤0.015 μg/mL) were susceptible to ceftaroline. Rates of susceptibility to ceftaroline among ESBL-negative Escherichia coli (n= 338), Klebsiella pneumoniae (n= 241), and Klebsiella oxytoca (n= 97) were 89.1% (MIC90, 1 μg/mL), 94.2% (MIC90, 0.5 μg/mL), and 99.0% (MIC90, 0.5 μg/mL), respectively.

Polyphenolic Secondary Metabolites Synergize the Activity of Commercial Antibiotics against Clinical Isolates of β-Lactamase-producing Klebsiella pneumoniae.

Emergence of worldwide antimicrobial resistance prompted us to study the resistance modifying potential of plant-derived dietary polyphenols, mainly caffeic acid, ellagic acid, epigallocatechin-3-gallate (EGCG) and quercetin. These compounds were studied in logical combination with clinically significant antibiotics (ciprofloxacin/gentamicin/tetracycline) against Klebsiella pneumoniae, after conducting phenotypic screening of a large number of clinical isolates and selecting the relevant strains possessing extended-spectrum β-lactamase (ESBL) and K. pneumoniae carbapenemase (KPC)-type carbapenemase enzymes only. The study demonstrated that EGCG and caffeic acid could synergize the activity of tested antibiotics within a major population of β-lactamase-producing K. pneumoniae. In spectrofluorimetric assay, ~17-fold greater ciprofloxacin accumulation was observed within K. pneumoniae cells pre-treated with EGCG in comparison with the untreated control, indicating its ability to synergize ciprofloxacin to restrain active drug-efflux. Further, electron micrograph of ESBL-producing K. pneumoniae clearly demonstrated the prospective efficacy of EGCG towards biofilm degradation.

In vitro activity of ceftaroline against bacterial pathogens isolated from skin and soft tissue infections in Europe, Russia and Turkey in 2012: results from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance programme.

The objective of this study was to analyse antimicrobial susceptibility testing data generated by the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) global surveillance programme for pathogens causing skin and soft tissue infections (SSTIs) in European countries in 2012. Confirmation of pathogen identity by MALDI-TOF and antimicrobial susceptibility testing following the CLSI broth microdilution method were performed by a central laboratory. Using CLSI breakpoint criteria, ceftaroline was active against MSSA (n = 1116; MIC90, 0.25 mg/L; 99.8% susceptible), MRSA (n = 1467; MIC90, 1 mg/L; 92.2% susceptible) and Streptococcus pyogenes (n = 312; MIC90, 0.008 mg/L; 100% susceptible). By CLSI interpretative criteria, two S. aureus isolates (2/2583, 0.08%) were ceftaroline resistant (MIC, ≥4 mg/L) and 114 isolates (114/2583, 4.4%) were ceftaroline intermediate (2 mg/L). By EUCAST interpretative criteria (MIC, >1 mg/L), 4.5% (116/2583) of S. aureus isolates were ceftaroline resistant. Most ceftaroline-non-susceptible isolates (81.0%, 94/116) were from Russia, Turkey, Italy and Hungary. Ceftaroline susceptibility was equal to or exceeded 99% for S. aureus isolates submitted by 7 of 17 countries. Against Escherichia coli (n = 349), Klebsiella pneumoniae (n = 215), Klebsiella oxytoca (n = 74) and Proteus mirabilis (n = 121), ceftaroline activity was dependent upon ESBL production. For ESBL-negative E. coli, K. pneumoniae, K. oxytoca and P. mirabilis, 87.5% (MIC90, 1 mg/L), 92.3% (MIC90, 0.5 mg/L), 93.2% (MIC90, 0.5 mg/L) and 85.1% (MIC90, 2 mg/L) of isolates were susceptible to ceftaroline, respectively. Ceftaroline demonstrated potent in vitro activity against a contemporary collection of bacterial pathogens from patients with SSTIs in European countries, Russia and Turkey. Surveillance programmes such as AWARE are essential to global efforts to improve antimicrobial stewardship.

In Vitro Activity of Ceftaroline against Staphylococcus aureus Isolated in 2012 from Asia-Pacific Countries as Part of the AWARE Surveillance Program.

Ceftaroline, the active metabolite of the prodrug ceftaroline-fosamil, is an advanced-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). This investigation provides in vitro susceptibility data for ceftaroline against 1,971 S. aureus isolates collected in 2012 from seven countries (26 centers) in the Asia-Pacific region as part of the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) program. Broth microdilution as recommended by the CLSI was used to determine susceptibility. In all, 62% of the isolates studied were MRSA, and the ceftaroline MIC90 for all S. aureus isolates was 2 μg/ml (interpretive criteria: susceptible, ≤1 μg/ml). The overall ceftaroline susceptibility rate for S. aureus was 86.9%, with 100% of methicillin-sensitive S. aureus isolates and 78.8% of MRSA isolates susceptible to this agent. The highest percentages of ceftaroline-nonsusceptible MRSA isolates came from China (47.6%), all of which showed intermediate susceptibility, and Thailand (37.1%), where over half (52.8%) of isolates were resistant to ceftaroline (MIC, 4 μg/ml). Thirty-eight ceftaroline-nonsusceptible isolates (MIC values of 2 to 4 μg/ml) were selected for molecular characterization. Among the isolates analyzed, sequence type 5 (ST-5) was the most common sequence type encountered; however, all isolates analyzed from Thailand were ST-228. Penicillin-binding protein 2a (PBP2a) substitution patterns varied by country, but all isolates from Thailand had the Glu239Lys substitution, and 12 of these also carried an additional Glu447Lys substitution. Ceftaroline-fosamil is a useful addition to the antimicrobial agents that can be used to treat S. aureus infections. However, with the capability of this species to develop resistance to new agents, it is important to recognize and monitor regional differences in trends as they emerge.

Activity of ceftaroline and comparators against pathogens isolated from skin and soft tissue infections in Latin America – results of AWARE surveillance 2012

As part of the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance program in 2012 the in vitro activity of ceftaroline and relevant comparator antimicrobials was evaluated in six Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico and Venezuela) against pathogens isolated from patients with hospital associated skin and soft tissue infections (SSTIs). The study documented that ceftaroline was highly active (MIC90 0.25mg/L/% susceptible 100%) against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus (MIC90 2mg/L/% susceptible 83.3%) and β-hemolytic streptococci (MIC90 0.008–0.015mg/L/% susceptible 100%). The activity of ceftaroline against selected species of Enterobacteriaceae was dependent upon the presence or absence of extended-spectrum β-lactamases (ESBLs). Against ESBL screen-negative Escherichia coli, Klebsiella pneumoniae, and Klebsiella oxytoca the MIC90 and percent susceptible for ceftaroline were (0.5mg/L/94.1%), (0.5mg/L/99.0%) and (0.5mg/L/91.5%), respectively. Ceftaroline demonstrated potent activity against a recent collection of pathogens associated with SSTI in six Latin American countries in 2012.

Prescription practices in acute pediatric infections and their implications on the worldwide antimicrobial resistance

A large proportion of antimicrobial agents are prescribed worldwide for acute respiratory infections, including colds, upper respiratory infections, acute bronchitis, pharyngo-tonsillitis, sinusitis, and acute otitis media [1–9]. Many of these infections are viral in nature, and antimicrobials are of no benefit. However, the widespread and inappropriate utilization of antimicrobials for such viral illnesses is the driving force behind the emergence of infections caused by antimicrobial drug-resistant organisms [10–12]. Antimicrobial drug – resistant strains of communityacquired pathogens, including Streptococcus pneumoniae, Haemophillus influenzae, and Staphylococcusaureus, have emerged as serious global health threats [13– 15]. In the United States the proportion of invasive infections caused by penicillin-nonsusceptible S. pneumoniae increased from 1% in 1992 to 27% in 2000 [10]. Multiple drug resistance of S. pneumoniae has also escalated in frequency as the proportion of S. pneumoniae isolates nonsusceptible to 3 classes of antimicrobial drugs increased from 7% in 1995 to 19% in 2000 [10].