A singular medical incident can alert health officials to an emerging, if not widespread, but possibly undetected publichealth concern.

Our issue contains a remarkable case of a ruptured hepatic abscess in a 3-year-old, which turned out to be MethicillinresistantStaphylococcus aureus (MRSA) by authors Torrico and Tarnate.The concern is that the infection is communityacquired,and the patient was immunocompetent. This sounds the alarm for the occurrence of antimicrobial resistance (AMR)in the communities and calls for a response from health authorities to investigate, analyze, and propose solutions for sucha sentinel event.

We need to support these efforts and, in this issue, we publish such work from our investigators. Antimicrobial resistanceis an urgent global health concern.The impact is magnified in low to middle-income countries where health risks are high,and health infrastructure is weak. Thus, it is imperative that determinants of AMR are scrutinized to allow crafting offocused strategies to combat the problem.

The article by Dela Cruz and Hernandez on the prevalence and practices of antibiotic misuse among adult residents ofRodriguez, Rizal, contributes to this analysis.The paper reveals a disturbing prevalence of self-medication and identifiesbarriers to accessing proper health education and care. This is a global problem, and the paper from Brazil relates the observationof community pharmacists of antibiotic misuse to the rise of antimicrobial resistance.

Dela Cruz and Hernandez recommend stricter antibiotic regulation, and this falls squarely into the scope of concernof another article in this issue, the “Research Needs in Philippine Pharmaceutical Sciences: A Qualitative Perspective fromRegulatory and Clinical Research Sectors of the Pharmaceutical Industry” by Pena and co-authors.Interestingly, whiledrug registration and clinical trials were the focus of the paper, it may be a desired expansion of the regulatory reach of theindustry to temper the use of antibiotics as it is being dispensed to end users.Antimicrobial stewardship involves ethicalpromotion of use and equitable access to appropriate treatment, and these concerns require the responsible participation of thepharmaceutical industry.

Health challenges are complex. The analysis of these challenges requires surveillance of literature for sentinel events, useof community-based research to investigate phenomena, and system mapping to identify relevant sectors to improve strategyand to involve relevant stakeholders.

We support this type of scholarship, which seeks to expand the focus from isolated clinical interventions towards placinga spotlight on relevant work that will lead to impactful reform of broad health ecosystems.

Human ; Child Preschool: 2-5 Yrs Old ; Therapeutics ; Staphylococcus Aureus ; Pharmaceutical Preparations ; Research Personnel ; Health Services Needs And Demand ; Methicillin-resistant Staphylococcus Aureus ; Antimicrobial Stewardship

Methicillin-resistantStaphylococcus aureus(MRSA) is an uncommon etiologic agent of hepatic abscess in children, particularly those without an underlying immunocompromised condition.

We describe a rare case of community-acquired MRSA (CA-MRSA) hepatic abscess with rupture into the anterior abdominal wall in an otherwise healthy 3-year-old Filipino male, manifesting as a one-week history of an enlarging epigastric mass accompanied by abdominal pain and fever. He was treated noninvasively with ciprofloxacin (intravenous at 10 mg/kg every 12 hours for 14 days followed by oral at 15 mg/kg every 12 hours for 28 days), and clindamycin (intravenous at 10 mg/kg every 6 hours for 14 days followed by oral at 10 mg/kg every 6 hours for 28 days), resulting in the resolution of the hepatic abscess and its associated symptoms.

CA-MRSA hepatic abscess is extremely rare in immunocompetent children, and an appropriate diagnostic approach involving imaging and culture studies is crucial in its diagnosis and management.

Human ; Child Preschool: 2-5 Yrs Old ; Therapeutics ; Staphylococcus Aureus ; Staphylococcus ; Residence Characteristics ; Research Report ; Dihydrotachysterol

Purulent pericarditis is a rare occurrence in the era of modern antibiotics. It is most often caused by organisms such as Staphylococcus aureus, Streptococcus pneumoniae, Viridans streptococci, Haemophilus influenzae and anaerobic bacteria with Streptococcus pyogenes (S.pyogenes) being a possible, though very uncommon etiology. This case represents an occurrence of S. pyogenes pericarditis in an apparently healthy female with no known immunocompromising condition. A 37-year-old female, married, real estate agent with no comorbidities came in for chest pain radiating to the upper back, relieved with leaning forward. Cardiac biomarker was normal, ECG demonstrated diffuse ST-segment elevation and PR segment depression, while imaging showed lobar pneumonia. Blood tests showed leukocytosis with neutrophilic predominance and workup for immunocompromised state was negative. The 2D echo showed large pericardial effusion with tamponade physiology. An urgent pericardiocentesis was done. Cultures grew Streptococcus pyogenes confirming the diagnosis of acute purulent pericarditis. Daily drainage of pericardial effusion, colchicine, ibuprofen was initiated together with antibiotics and the patient had resolution of pericardial effusion. Acute pyogenic pericarditis with cardiac tamponade is a rare but serious condition that requires prompt recognition and intervention. Early diagnosis, through a combination of clinical suspicion, ECG and echocardiography is crucial for initiating timely treatment.

Human ; Female ; Adult: 25-44 Yrs Old ; Viridans Streptococci ; Streptococcus Pyogenes ; Streptococcus Pneumoniae ; Staphylococcus Aureus ; Streptococcal Infections ; Electrocardiography ; Echocardiography ; Early Diagnosis

BACKGROUND AND OBJECTIVES

Staphylococcus aureus poses a significant public health threat globally, where both community and hospital-acquired infections are prevalent. The escalating antimicrobial resistance highlights the urgent need for alternative therapies. Hence, traditional medicine using plant extracts offers a potential avenue for novel antibacterial agents. This systematic review aimed to evaluate the existing literature on the antibacterial properties of Philippine plants against S. aureus to provide focus on drug development of a plant-derived antibacterial for this pathogen.

METHODS

Following PRISMA guidelines, a comprehensive search was conducted in PubMed/Medline, SCOPUS, and Herdin databases. Inclusion criteria encompassed in-vitro studies evaluating the antibacterial activity of crude plant extracts sourced from Philippines plants against S. aureus. Data extraction and quality assessment were performed independently by two reviewers, with discrepancies resolved by the third and fourth reviewers.

RESULTS

Of the 413 initial studies identified, nine (9) met the eligibility criteria. The highest zone of inhibition was demonstrated by Lippia micromera L. leaf essential oil at 26.3±1.5 mm, while moderate antibacterial activity was shown by essential oils from Alpinia elegans, Piper quinqueangulatum, and Alpinia cumingii at MIC values of 512 µg/mL, 512 µg/mL, and 1,024 µg/mL, respectively. Other Philippine plants showed a wide range of activity, with MIC values between 50 ?g/mL and 25 mg/mL, MBC values from 78 to 5000 ?g/mL, and ZOI ranging from 5 to 38 mm. However, the overall quality of evidence in these other studies are compromised by bias and incomplete reporting.

CONCLUSION

Leaf essential oils from Alpinia elegans, Piper quinqueangulatum, and Alpinia cumingii demonstrated moderate antibacterial activity against S. aureus. Additionally, the essential oils of Lippia micromera L., Plectranthus amboinicus Lour. Spreng, and Cymbopogon citratus exhibited antibacterial activity against both S. aureus and Methicillin-resistant S. aureus (MRSA) in disk diffusion assays. Majority of the studies gathered had high risk of bias according to the quality assessment criteria tool used in the study. Thus, this systematic review also emphasizes the need for improved methodological rigor on reported in-vitro antibacterial studies.

Staphylococcus ; Staphylococcus Aureus ; Systematic Review

BACKGROUND AND OBJECTIVE

The human nasal passages host major human pathogens. Recent research suggests that the microbial communities inhabiting the epithelial surfaces of the nasal passages play a key factor in maintaining a healthy microenvironment by affecting both resistance to pathogens and immunological responses. Colonization of the nasal cavity by different pathogens such as Staphylococcus aureus and Klebsiella aerogenes, is associated with a higher postoperative infection morbidity. Povidone-iodine (PVP-I) as an antiseptic has been proven to display high antibacterial, antiviral, and antifungal properties even at low concentrations, and was shown to be effective in the control of infections to limit their impact and spread. It can be used as a topical antiseptic for skin decontamination and wound management, as a nasal spray, or as a gargle. There are different methods in testing the efficacy of potential antimicrobial suspensions. This study aimed to determine the concentration of PVP-I that is most effective in nasal decolonization using microsuspension test and colorimetric minimum inhibitory concentration (MIC) determination assays, resazurin microtiter assay (REMA), and Dey-Engley (D/E) neutralizer assay. The findings of this study will contribute to knowledge regarding the intended use of PVP-I in microbial control, particularly in bacterial infections.

METHODS

Several dilutions (2.0%, 1.0%, 0.5%, 0.25%, 0.1% and 0.09%) of commercially bought 10% (10 mg per 100 ml) povidone-iodine were prepared and tested against a standardized inoculum (1x105) of Staphylococcus aureus and Klebsiella aerogenes at different contacttimes (5 seconds, 10 seconds, 30 seconds, 1 minute, and 5 minutes). Microdilution suspension test was performed to determine the log reduction per variable, while REMA and D/E neutralizer assay were used to determine the MIC. A value of greater than or equal to 5 log reduction was considered effective for microdilution suspension test. Estimates of agreement statistics were used to interpret the results of the assay in which the overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen’s kappa statistics were calculated.

RESULTS

Povidone-iodine concentration of 0.25% exhibited ?5 log reduction against K. aerogenes at the minimum contact time of 5 seconds. On the other hand,  a slightly higher PVP-I concentration was required to achieve ?5 log reduction for S. aureus at 0.5% concentration and a minimum contact time of 1 minute. There was an observed concordance of the results of REMA and D/E neutralizer as MIC colorimetric indicators, which yielded an overall test percent agreement of 90.30% (95% CI: 84.73–94.36), and a strong level of agreement (? = 0.8, pCONCLUSION

Low povidone-iodine concentrations (i.e., 0.5% against S. aureus and 0.25% against K. aerogenes) were observed to have bactericidal activity of at least 5 log reduction as rapid as the minimum contact time of 5 seconds. Furthermore, D/E and REMA, as colorimetric indicators, had comparable performance (OPA = 90.30%; ? = 0.8, p
Human ; Bacteria ; Povidone-iodine ; Microbial Sensitivity Tests ; Anti-infective Agents, Local ; Enterobacter Aerogenes ; Staphylococcus Aureus

BACKGROUND AND OBJECTIVE

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of hospital and community-acquired infections, showing antimicrobial resistance (AMR), which is an increasing public health concern. One of the commonly-used methods to evaluate resistance include the Kirby-Bauer disk diffusion method. However, this test is found to be time-consuming, lacking in terms of mechanization and automation, alongside its non-applicability to certain antibiotics such as vancomycin. Thus, the Clinical Laboratory Standards Institute (CLSI) recommends using the broth microdilution method in the evaluation of antibacterial activities against S. aureus. A rapid laboratory identification of MRSA is important in the treatment of patients. Therefore, this study aims to optimize and evaluate the effectiveness of a rapid microplate assay using resazurin dye as a colorimetric indicator in determining antibacterial activity against clinical isolates of MRSA and methicillin-susceptible S. aureus (MSSA).

METHODS

Clinical isolates of MRSA and MSSA were obtained from the Philippine General Hospital (PGH) Microbiology Section, and American Type Culture Collection (ATCC) controls of both strains (ATCC 25923 and ATCC 43300) were acquired. These were then subjected to identification and confirmation procedures. A standardization of bacterial inoculum was performed by comparing its 24-hr growth in Mueller Hinton Broth to 0.5 McFarland Standard. The resazurin microplate assay (REMA) was set-up using two-fold serial dilution of control antibiotics such as oxacillin, vancomycin, and cefoxitin. Each plate was inoculated with standardized bacterial growth of controls and clinical isolates. To determine the time needed for the reduction of the resazurin dye, a qualitative assessment was conducted by comparing the reaction time between a 6.75 mg/mL dye with a 0.01 mg/mL dye. The plates were also subjected to different incubation times and dye concentrations, and the optical densities of the plates were compared using a microplate reader.

RESULTS

Results showed that there were no significant differences between the optical densities of the wells of those incubated for 5 hours and for 24 hours (p >0.05). Furthermore, there was a significant reduction in the reaction time of the dye (from 18 hours to 1 hour) when the dye concentration was reduced from 6.75 mg/mL to 0.01 mg/mL. The optimized REMA showed a significant difference between the minimum inhibitory concentrations (MICs) of the different antibiotics against the control and isolate strains of MRSA and MSSA, showing a W of -2.98 (pCONCLUSION

Based on the results presented, the researchers determined the optimal condition for the resazurin microtiter assay, which was 0.01 g/mL concentration of resazurin dye, at a 5-hour incubation period. This study has shown that an optimized REMA is an efficient and fast method to determine the antimicrobial activities of oxacillin, cefoxitin, and vancomycin against MRSA and MSSA.

Methicillin-resistant Staphylococcus Aureus

Otitis media is an infection of the middle ear mainly caused by bacteria, and current treatments rely heavily on antibiotics. However, the emergence of antibiotic-resistant bacterial strains seriously affects their efficacy. In our study, we found that extracellular vesicles (EVs) derived from human natural killer cells (NKs) inhibit the proliferation of both standard and levofloxacin (LVX)-resistant strains of Staphylococcus aureus in a dose-dependent manner. Moreover, compared to LVX, EVs were more effective at reducing effusion and rescuing hearing thresholds in animal models. For LVX-sensitive strains, EVs were significantly more effective in terms of curative time but not curative rate. For LVX-resistant strains, EVs were significantly more effective in terms of both curative rate and curative time when applied alone or applied jointly with LVX. In summary, we found that NK EVs are highly effective in treating otitis media, providing an alternative approach for treating this common disease.
Killer Cells, Natural/metabolism* ; Exosomes/metabolism* ; Animals ; Humans ; Otitis Media/therapy* ; Staphylococcus aureus/drug effects* ; Disease Models, Animal ; Anti-Bacterial Agents/pharmacology* ; Levofloxacin/pharmacology*

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

OBJECTIVE: To explore the mechanism of antibiotic delivery system targeting bacterial biofilm with linezolid (LZD) based on ε-poly- L-lysine (ε-PLL) and cyclodextrin (CD) (ε-PLL-CD-LZD), aiming to enhance antibiotic bioavailability, effectively penetrate and disrupt biofilm structures, and thereby improve the treatment of bone and joint infections. METHODS: ε-PLL-CD-LZD was synthesized via chemical methods. The grafting rate of CD was characterized using nuclear magnetic resonance. In vitro biocompatibility was evaluated through live/dead cell staining after co-culturing with mouse embryonic osteoblast precursor cells (MC3T3-E1), human umbilical vein endothelial cells, and mouse embryonic fibroblast cells (3T3-L1). The biofilm-enrichment capacity of ε-PLL-CD-LZD was assessed using Staphylococcus aureus biofilms through enrichment studies. Its biofilm eradication efficacy was investigated via minimum inhibitory concentration (MIC) determination, scanning electron microscopy, and live/dead bacterial staining. A bone and joint infection model in male Sprague-Dawley rats was established to validate the antibacterial effects of ε-PLL-CD-LZD. RESULTS: In ε-PLL-CD-LZD, the average grafting rate of CD reached 9.88%. The cell viability exceeded 90% after co-culturing with three types cells. The strong biofilm enrichment capability was observed with a MIC of 2 mg/L. Scanning electron microscopy observations revealed the effective disruption of biofilm structure, indicating potent biofilm eradication capacity. In vivo rat experiments demonstrated that ε-PLL-CD-LZD significantly reduced bacterial load and infection positivity rate at the lesion site ( P<0.05). CONCLUSION The ε-PLL-CD antibiotic delivery system provides a treatment strategy for bone and joint infections with high clinical translational significance. By effectively enhancing antibiotic bioavailability, penetrating, and disrupting biofilms, it demonstrated significant anti-infection effects in animal models.
Biofilms/drug effects* ; Animals ; Anti-Bacterial Agents/pharmacology* ; Polylysine/chemistry* ; Cyclodextrins/administration & dosage* ; Humans ; Linezolid/pharmacology* ; Staphylococcus aureus/physiology* ; Rats, Sprague-Dawley ; Mice ; Rats ; Male ; Drug Delivery Systems ; Staphylococcal Infections/drug therapy* ; Microbial Sensitivity Tests ; Human Umbilical Vein Endothelial Cells ; Osteoblasts/cytology*

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure