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Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a surge in SSI and common antibiotics are proving to be ineffective against SSI. Antimicrobial peptides (AMPs) can be a potential solution to prevent SSI because of their broad spectrum of antimicrobial activities. In this study, naturally sourced AMPs were studied along with microfibers, fabricated by a novel wet-spinning method using sodium alginate and polycaprolactone. Afterward, fibers were functionalized by the catechol groups of dopamine immobilizing nucleophilic AMPs on the surface. Conjugation between PCL and alginate resulted in fibers with smooth surfaces improving their mechanical strength via hydrogen bonds. Having an average diameter of 220 μm, the mechanical properties of the fiber complied with USP standards for suture size 3-0. Engineered microfibers were able to hinder the growth of Proteus spp., a pathogenic bacterium for at least 60 hours whereas antibiotic ceftazidime failed. When subjected to a linear incisional wound model study, accelerated healing was observed when the wound was closed using the engineered fiber compared to Vicryl. The microfibers promoted faster re-epithelialization compared to Vicryl proving their higher wound healing capacity.

The development of a rapid hemostat through a facile method with co-existing antibacterial activity and minimum erythrocyte lysis property stands as a major requirement in the field of hemostasis. Herein, a series of novel microparticle hemostats were synthesized using chitosan, different hydrothermally-treated starches, and cross-linked with tannic acid (TA) simultaneously in an unoxidized environment via ionotropic gelation method. Hemostats' comparative functional properties, such as adjustable antibacterial and erythrocyte compatibility upon various starch additions were evaluated. The in vivo hemostatic study revealed that the developed hemostats for mouse liver laceration and rat tail amputation had clotting times (13 s and 38 s, respectively) and blood loss (51 mg and 62 mg, respectively) similar to those of Celox™. The erythrocyte adhesion test suggested that erythrocyte distortion can be lowered by modifying the antibacterial hemostats with different starches. The broad-spectrum antibacterial efficacy of the hemostats remained intact against S. aureus (>90 %), E. coli (>80 %), and P. mirabilis bacteria upon starch modification. They also demonstrated high hemocompatibility (<3 % hemolysis ratio), moderate cell viability (>81 %), in vivo biodegradation, and angiogenesis indicating adequate biocompatibility and wound healing. The developed hemostats hold significant promise to be employed as rapid hemostatic agents for preventing major bleeding and bacterial infection in emergencies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals., Methods: Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression., Results: Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent., Conclusions: This survey suggested a high prevalence of HAIs and AMU in Singapore's acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Acute cough is a common reason to prescribe antibiotics in primary care. This study aimed to explore help-seeking and antibiotic prescribing for acute cough in Chinese primary care population. This is a prospective multicentre observational study that included adults presenting with acute cough. Clinicians recorded patients' presenting symptoms, examination findings and medication prescription. Patients completed symptom diaries for up to 28 days by charting their symptom severity and recovery. Adjusted binary logistic regression models identified factors independently associated with antibiotic prescription. Primary care clinicians (n=19) recruited 455 patients. A total of 321 patients (70.5%) returned their completed symptom diaries. Concern about illness severity (41.6%) and obtaining a prescription for symptomatic medications (45.9%), rather than obtaining a prescription for antibiotics, were the main reasons for consulting. Antibiotics were prescribed for 6.8% (n=31) of patients, of which amoxicillin was the most common antimicrobial prescribed (61.3%), as it was associated with clinicians' perception of benefit from antibiotic treatment (odds ratio (OR): 25.9, 95% confidence interval (CI): 6.7-101.1), patients' expectation for antibiotics (OR: 5.1, 95% CI: 1.7-11.6), anticipation (OR: 5.1, 95% CI: 1.6-15.0) and request for antibiotics (OR 15.7, 95% CI: 5.0-49.4), as well as the severity of respiratory symptoms (cough, sputum, short of breath and wheeze OR: 2.7-3.7, all P<0.05). There was a significant difference in antibiotic prescription rates between private primary care clinicians and public primary care clinicians (17.4 vs 1.6%, P=0.00). Symptomatic medication was prescribed in 98.0% of patients. Mean recovery was 9 days for cough and 10 days for all symptoms, which was not significantly associated with antibiotic treatment. Although overall antibiotic-prescribing rates were low, there was a higher rate of antibiotic prescribing among private primary care clinicians, which warrants further exploration and scope for education and intervention.

Introduction: Chronic wounds represent a major health burden worldwide. It has been hypothesized that the polymicrobial nature of wounds plays an important role in their healing process. Thus, a review of pathogen frequency and susceptibility patterns in wounds is necessary to provide appropriate guidelines for antimicrobial usage., Methodology: In this study, microbiota and antimicrobial resistance in both acute and chronic wound patients treated at the University of Malaya Medical Centre, Malaysia, were compared. Wound swabs from 84 patients with acute wounds and 84 patients with chronic wounds were collected. The specimens were cultured using standard microbiological techniques. Isolates were then tested for antibiotic sensitivity with the broth microdilution method., Results: Of 210 pathogenic bacteria isolates, Staphylococcus aureus (49; 23.3%) and Pseudomonas aeruginosa (31; 14.8%) were the most prevalent bacteria found in wounds. Staphylococcus aureus was found significantly more often in patients with chronic wounds (41; 48.8%) than in patients with acute wounds (8; 9.5%), while Staphylococcus epidermidis was found predominantly in acute wounds (15; 17.9%). At the time of study, patients with chronic wounds (58.3%) had received more antibiotic treatments in the past previous 12 months compared with patients with acute wounds (16.7%). In the antibiotic susceptibility test, Staphylococcus spp. revealed highest resistance towards penicillin and ampicillin. Isolates showed no decrease in susceptibility against a number of newly developed antibiotics (linezolid, daptomycin, and tigecycline)., Conclusions: Our finding showed that bacteria diversity and antimicrobial-resistant strains are more frequently found in chronic wounds than in acute wounds.

Objective: Treatments with sequential therapy (SEQ) or bismuth quadruple (QUAD) therapy have been proposed as empirical firstline regimens for Helicobacter pylori. We compared the efficacy and tolerability of 10 day SEQ with 10 day modified QUAD as both firstline and secondline treatments for H pylori in a randomised crossover study., Design: H pylori positive and treatment naïve patients were randomly assigned to receive either 10 day SEQ (esomeprazole for 10 days, amoxicillin for an initial 5 days, followed by clarithromycin and metronidazole for a subsequent 5 days) or modified QUAD (esomeprazole, bismuth subcitrate, tetracycline and metronidazole). H pylori eradication was confirmed by urea breath test at 8 weeks. Patients who failed the initial assigned treatment were crossed over to receive the alternate regimen. The primary outcome was eradication rates of firstline treatment by intention to treat (ITT) and per protocol (PP) analyses., Results: 357 patients were randomised to receive either SEQ or QUAD. The PP eradication rates of the SEQ and QUAD groups were 95.2% and 98.8%, respectively (p=0.10). Based on ITT analysis, the corresponding eradication rates were 89.4% and 92.7%, respectively (p=0.36). Eight (4.8%) patients in the SEQ and two (1.2%) patients in the QUAD who failed the firstline treatment were crossed over to the alternate regimen with 100% retreatment success. The overall incidence of adverse events was higher in the QUAD (16.7%) than in the SEQ (8.1%; p=0.032) group., Conclusions: Ten day sequential and modified bismuth quadruple therapies are both highly effective as empirical firstline therapies for H pylori in Chinese patients., Clinicaltrialsgov: NCT 01760824., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Polyelectrolyte multilayer films assembled from a hydrophobic N-alkylated polyethylenimine and a hydrophilic polyacrylate were discovered to exhibit strong antifouling, as well as antimicrobial, activities. Surfaces coated with these layer-by-layer (LbL) films, which range from 6 to 10 bilayers (up to 45 nm in thickness), adsorbed up to 20 times less protein from blood plasma than the uncoated controls. The dependence of the antifouling activity on the nature of the polycation, as well as on assembly conditions and the number of layers in the LbL films, was investigated. Changing the hydrophobicity of the polycation altered the surface composition and the resistance to protein adsorption of the LbL films. Importantly, this resistance was greater for coated surfaces with the polyanion on top; for these films, the average zeta potential pointed to a near neutral surface charge, thus, presumably minimizing their electrostatic interactions with the protein. The film surface exhibited a large contact angle hysteresis, indicating a heterogeneous topology likely due to the existence of hydrophobic-hydrophilic regions on the surface. Scanning electron micrographs of the film surface revealed the existence of nanoscale domains. We hypothesize that the existence of hydrophobic/hydrophilic nanodomains, as well as surface charge neutrality, contributes to the LbL film's resistance to protein adsorption.

The global threat posed by drug-resistant strains of Mycobacterium tuberculosis demands a greater understanding of the genetic basis and molecular mechanisms that govern how such strains develop resistance against various antituberculous drugs. In this report, we examine a new genetic basis for resistance to one of the oldest and most widely used second-line drugs employed in tuberculosis therapy, streptomycin (SM). This marker for SM resistance was first discovered on the basis of genomic data obtained from drug-resistant M. tuberculosis strains collected in Japan, wherein an association was observed between SM resistance and a mutation in gidB, a putative 16S rRNA methyltransferase. By evaluating an isogenic ΔgidB mutant strain constructed from strain H37Rv, we demonstrate the causal role of gidB in conferring a low-level SM-resistant phenotype in M. tuberculosis with a 16-fold increase in the MIC over the parent strain. Among clinical isolates, the modest increase in SM resistance conferred by a gidB mutation leads to an MIC distribution of gidB mutation-containing strains that spans the recommended SM breakpoint concentration currently used in drug susceptibility testing protocols. As such, some gidB mutation-containing isolates are found to be SM sensitive, while others are SM resistant. On the basis of a pharmacodynamic analysis and Monte Carlo simulation, those isolates that are found to be SM sensitive should still respond favorably to SM treatment, while nearly half of those found to be SM resistant will likely respond poorly. This report provides the first microbiological evidence for the contribution of gidB in streptomycin resistance and examines the clinical implications of mutations in the gidB gene.

Hydrophobic polycations previously developed by us efficiently kill E. coli and Staphylococcus aureus on contact. As visualized by electron microscopy herein, these pathogenic bacteria incur marked morphological damage from the exposure to these N-alkylated-polyethylenimine "paints" which results in the leakage of an appreciable fraction of the total cellular protein. The quantity and composition of that leaked protein is similar to that released upon traditional lysozyme/EDTA treatment, thus providing insights into the mechanism of action of our microbicidal coatings.

In this work, we designed contact-killing ionically cross-linked polymeric thin films using Layer-by-Layer (LbL) technology. A polycation, N,N-dodecyl,methyl-polyethylenimine, with microbicidal activity was layered with a polyanion, such as poly(acrylic acid), to create LbL films highly effective against both airborne and waterborne Escherichia coli and Staphylococcus aureus (Gram negative and positive bacteria, respectively), as well as influenza A/WSN (H1N1) virus. The dependence of the microbicidal activity on the pH during and post-assembly of LbL film formation, the nature of the polycation and polyanion, the number of layers in the LbL film, and other experimental variables was investigated quantitatively., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Recent studies have suggested the eradication rate for Helicobacter pylori infection with standard amoxycillin-clarithromycin-containing triple therapy as first-line treatment have fallen below 80%. Levofloxacin-containing triple therapy was proposed as an alternative. The aim of this study is to compare the efficacy and tolerability of the standard 7-day clarithromycin-containing triple therapy against the 7-day levofloxacin-containing triple therapy, and to assess whether the classical triple therapy is still valid as empirical first-line treatment for H. pylori infection in Hong Kong., Methods: Three hundred consecutive H. pylori-positive patients were randomized to receive either 1 week of EAL (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and levofloxacin 500 mg daily) or EAC (esomeprazole 20 mg b.d., amoxycillin 1 g b.d., and clarithromycin 500 mg b.d.). H. pylori status was rechecked by (13)C-urea breath test 6 weeks after treatment. Patients who failed either of the first-line eradication therapy were invited to undergo H. pylori susceptibility testing., Results: H. pylori eradication was achieved in 128 of 150 (85.3%) patients in EAL and 139 of 150 (92.7%) patients in EAC groups, respectively (p = .043), for both intention-to-treat and per-protocol analysis. More patients in the clarithromycin- than the levofloxacin-containing therapy group developed side effects from the medication (21.3% vs 13.3%, p = .060). Nine patients (six from the EAL group and three from the EAC group) who failed their corresponding eradication therapy returned for susceptibility testing. All nine isolates were highly resistant to levofloxacin (minimum inhibitory concentration or MIC > 32 microg/mL), whereas only two of the six isolates from the EAL group were resistant to clarithromycin (MIC > 0.5 microg/mL)., Conclusions: The standard 7-day clarithromycin-containing triple therapy is still valid as the most effective empirical first-line eradication therapy for H. pylori infection in Hong Kong, as prevalence of primary resistance of H. pylori to amoxycillin and clarithromycin remains low. Patients who failed their empirical first-line eradication therapy should undergo H. pylori susceptibility testing to guide further treatment.

Two alarming trends threaten the future utility of antimicrobial agents: rise of antimicrobial resistance and decline in development of new antibiotics. The continuing emergence and spread of antimicrobial-resistant microbes--a global public health issue--exacerbates the problem of paucity of new antimicrobial agents. Singapore's public sector hospitals currently have some of the highest rates of antimicrobial resistance worldwide, evolving with surprising speed over the past two decades. Because there was no systematic surveillance until fairly recently, this healthcare problem has not been emphasised. In contrast, it is difficult to assess the scale of antimicrobial resistance in the community in view of the lack of recent research, although indirect evidence suggests that this is also a source of concern. A panel comprising representatives from multiple professional healthcare societies was convened to address the issue of antimicrobial resistance in Singapore, focusing on the conservation of antibiotics against resistance. From a review of the medical literature, potentially successful strategies involve facilitating prudent and appropriate use of antimicrobial agents in tandem with other interventions in infection control. Presently, there is a lack of data on the appropriate use of antibiotics in Singapore. The recommendations of the panel are: The professions should look into ways and means to support systematic data collection on antibiotic use and appropriateness of use; The Ministry of Health should take a more active and positive role in regulating antibiotic usage; Hospitals should actively support effective antimicrobial stewardship programmes; Educators should coordinate programmes to give greater emphasis on appropriate antimicrobial prescription, and support good clinical practice; and, Local and regional branches of pharmaceutical companies should adopt the Pharmaceutical Research and Manufacturers of America's updated code of conduct on interactions with physicians as a step towards re-aligning the industry-physician relationship in the direction of educational and informational support.

Aim: Pyogenic liver abscesses result in substantial morbidity and mortality. Antimicrobial regimens using sequential intravenous/oral therapy may reduce the length of hospital stay. In this retrospective analysis, the efficacy of continuous intravenous antibiotic therapy (group I) vs. sequential intravenous/oral antibiotic therapy (group II) was studied in patients with pyogenic liver abscess., Methods: One hundred and twelve consecutive patients (55 in group I and 57 in group II) with pyogenic liver abscess were analysed. Clinical response, length of hospital stay and relapse rates were examined., Results: Group II had a significantly shorter duration of intravenous antibiotic treatment (3.2 weeks vs. 5.9 weeks, P < 0.01) and a shorter length of hospital stay (28 days vs. 42 days, P < 0.01) when compared to group I. Oral antibiotics were prescribed for a median duration of 2.9 weeks in group II after discharge. No relapse occurred within 6 weeks after the completion of treatment in both groups. The cost of therapy was significantly lower in group II than in group I by 33%., Conclusions: A sequential intravenous/oral antibiotic regime is a safe and effective treatment for pyogenic liver abscess. This reduces the cost of therapy and the length of hospital stay.