Comparison of the Effect of Different Treatment Doses of Intrastromal Vancomycin in a Rabbit Model of Methicillin-Resistant Staphylococcus Aureus (MRSA) Keratitis.

PURPOSE: To compare the effect of different doses of vancomycin on a rabbit model of MRSA keratitis. METHODS: Twenty-four eyes of 24 New-Zealand White rabbits were included in the study. MRSA keratitis was applied to 24 left eyes of 24 New Zealand rabbits. Twenty-four hours after MRSA inoculation; 0.5 mg/0.1 mL, 1 mg/0.1 mL, and 2 mg/0.1 mL and balanced salt solution were administered to 6 rabbits in 4 groups, respectively. RESULTS: The effect of different doses of vancomycin on reducing bacterial load was found to be statistically significant when each was compared to the control group (p = 0.006). When comparing the dosages with each other, no superiority was shown (p = 0.297, p = 0.749, p = 0.262 respectively). There was a significant increase in the posttreatment total clinical score in the control and 2 mg/0.1 mL groups compared to the pretreatment score (p = 0.001, p = 0.001 respectively). CONCLUSION: It is emphasized that necessary treatment can be achieved by administering less antibiotic (0.5 mg/0.1 mL) to the corneal intrastromal area.

Isolated Acromioclavicular Joint Septic Arthritis: A Case Report and Review of Literature.

A 60-year-old diabetic patient presented with acute pain and swelling localized to the left acromioclavicular joint. Laboratory and radiological investigations revealed the presence of pus in the left acromioclavicular joint along with bony erosion of the lateral end of the left clavicle. She was treated with open arthrotomy, debridement, and appropriate antibiotics for the causative methicillin-resistant Staphylococcus aureus (MRSA) infection. Prompt diagnosis and timely intervention can reduce the morbidity and mortality due to septic arthritis. We conducted a review of the literature on patients treated for isolated septic arthritis of the acromioclavicular joint.

A Rare Neonatal Infection: Methicillin-Resistant Staphylococcus aureus (MRSA) Orbital Cellulitis.

We present a case of orbital cellulitis as a rare cause of late-onset neonatal sepsis in a 4-week-old infant. Although ample literature describes orbital cellulitis in pediatric age groups, community-acquired orbital cellulitis as a cause of late-onset neonatal sepsis has not been well-described. We report one case of late neonatal sepsis in which orbital cellulitis and subsequent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia were found. This case emphasizes the importance of early recognition of orbital cellulitis in neonates and awareness of this unique cause of sepsis.

An Unusual Presentation of Monofocal Methicillin-Resistant Staphylococcus aureus Hepatic Abscess in an Otherwise Healthy Man.

A hepatic abscess is the collection of suppurative matter within the parenchyma of the liver. While most pyogenic liver abscesses (PLAs) are polymicrobial in nature, some rare cases are caused by methicillin-resistant Staphylococcus aureus (MRSA). We present a case of a 43 year-old male without evident exposures who presented with abdominal pain and via CT imaging was found to have monofocal MRSA hepatic abscess. An ultrasonography (US)-guided abscess drainage along with a pigtail catheter placement was performed along with antibiotic initiation. This article emphasizes the clinical manifestations of hepatic abscesses and employs literature reviews to offer a comprehensive approach to managing these patient populations.

5-aminolevulinic acid photodynamic therapy for chronic wound infection in rats with diabetes.

Recent research indicated that ulcers and peripheral vascular disease resulting from drug-resistant bacterial infections are the main causes of delayed healing in chronic diabetic wounds. 5-Aminolevulinic acid (ALA) is a second-generation endogenous photosensitizer. The therapeutic effect and mechanism of ALA-mediated photodynamic therapy (ALA-PDT) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds in diabetic rats were investigated in this study. The results revealed the promising antibacterial effects of ALA-PDT MRSA in vitro, with a minimum inhibitory concentration and minimum bactericidal concentration of 250 and 500 µM, respectively. ALA-PDT also changed the permeability and structural integrity of bacterial cell membranes by producing reactive oxygen species. Meanwhile, ALA-PDT accelerated wound healing in MRSA-infected diabetic rats, with 5 % ALA-PDT achieving complete sterilization in 14 days and wound closure in 21 days. Treatment with 5 % ALA-PDT additionally improved the histopathological appearance of skin tissue, as well as fibrosis, inflammatory cytokine release, and angiogenesis-related protein expression. These findings indicated that ALA-PDT significantly promoted the healing of MRSA-infected wounds in diabetic rats by eliminating bacteria, inhibiting inflammation, generating granulation tissues, promoting neovascularization, and restoring damaged nerves. In addition, the healing mechanism was related to the activation of inflammatory and angiogenesis pathways through the regulation of tumor necrosis factor-alpha and interleukin-6 expression and upregulation of CD206, CD31, and VEGF. These findings underscored the potential role of ALA-PDT in promoting the healing of chronic diabetic wounds.

Atypical cutaneous manifestations of methicillin resistant Staphylococcus aureus infections in two immunocompetent pediatric patients: Case reports and review of the literature.

Although many clinical variants of Staphylococcus aureus infection are well-recognized, atypical presentations may mimic other conditions. We describe two cases of atypical S. aureus infections in pediatric patients: a S. aureus infection presenting with a vesicopustular rash mimicking varicella zoster virus and a case of multifocal panniculitis. Both of these cases were specifically caused by methicillin-resistant S. aureus (MRSA). Additional cases of atypical S. aureus infections and presenting features from the current literature are also discussed.

A Single Lung Abscess Caused by Panton-Valentine Leukocidin-Producing Methicillin-Resistant Staphylococcus aureus.

This case report presents a rare occurrence of a single lung abscess caused by Panton-Valentine leukocidin (PVL)-producing methicillin-resistant Staphylococcus aureus (MRSA) in a 38-year-old immunocompetent man. The patient, of Southeast Asian origin, presented with symptoms of fever, chest pain, cough, and shortness of breath following a recent flu-like illness. Imaging indicated a cavitary lung lesion in the left lower lobe, suggestive of a lung abscess. Initial antibiotic treatment failed, and drainage of the abscess confirmed MRSA with the PVL gene, indicating a community-acquired MRSA infection. The patient received intravenous vancomycin followed by oral linezolid, leading to the resolution of the abscess. Contact tracing and decolonization measures were implemented. This case highlights the importance of considering PVL-producing S. aureus as a potential pathogen in severe necrotizing pneumonia or sepsis and underscores the need for prompt diagnosis, appropriate antibiotic therapy, and infection control measures in managing such infections.

The Clinical Characteristics and Antimicrobial Resistance of Staphylococcus aureus Isolated from Patients with Staphylococcal Scalded Skin Syndrome (SSSS) in Southwestern China.

Staphylococcal scalded skin syndrome (SSSS) is a rare, toxin-mediated, desquamating bacterial infectious dermatosis. So far, data from Southwestern China is scarce. This study aimed to investigate the clinical characteristics of SSSS patients in our hospital, the relative proportion of methicillin-resistant Staphylococcus aureus (MRSA) in skin and soft tissue secretions, and the drug sensitivity of S. aureus to better assist dermatologists in the diagnosis and treatment of SSSS. We reviewed the demographic characteristics, clinical manifestations, treatment regimens, therapeutic efficacy, laboratory test results, drug sensitivity, and outcome data of 79 SSSS patients from January 2012 to December 2021. Statistical analysis was performed using t tests and chi-square tests. Among the 79 SSSS patients, MRSA was detected in 35 (44.3%) isolates: 34 community-acquired (CA)-MRSA (97.1%) and 1 hospital-acquired (HA)-MRSA. The SSSS incidence increased annually from 2012 to 2014 and then decreased gradually after peaking in 2015. All the isolates were sensitive to vancomycin, tigecycline, linezolid, moxifloxacin, levofloxacin, and ciprofloxacin; were completely resistant to penicillin; and had low sensitivity to clindamycin and erythromycin. Interestingly, the sensitivity of MRSA to tetracycline increased annually after 2015. The resistance rates to common drugs previously used to treat SSSS increased. These findings may accelerate diagnosis and improve empirical antibiotic use, suggesting that clinicians should prescribe drugs according to antimicrobial susceptibility.

miR-155 promotes Th17 differentiation by targeting FOXP3 to aggravate inflammation in MRSA pneumonia.

BACKGROUND: Previous researches have clarified that miR-155 is increased in methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and modulates Th9 differentiation. Like Th9 cells, Th17 cells were also a subset of CD4+ T cells and involved in MRSA pneumonia progression. This work aimed to investigate the role and mechanism of miR-155 in Th17 differentiation. METHODS: Bronchoalveolar lavage fluid (BALF) was collected from children with MRSA pneumonia and bronchial foreign bodies. MRSA-infected murine model was established followed by collecting BALF and lung tissues. qRT-PCR, ELISA and flow cytometry were performed to examine the mRNA expression and concentration of IL-17 and the number of Th17 cells in above samples. HE and ELISA were used to evaluate inflammatory responses in lung. Furthermore, CD4+ T cells were isolated from BALF of children for in vitro experiments. After treatments with miR-155 mimic/inhibitor, the roles of miR-155 in Th17/IL-17 regulation were determined. The downstream of miR-155 was explored by qRT-PCR, western blotting, dual luciferase reporter analysis and RIP assay. RESULTS: The levels of IL-17 and the proportion of Th17 cells were increased in children with MRSA pneumonia. A similar pattern was observed in MRSA-infected mice. On the contrary, IL-17 neutralization abolished the activation of Th17/IL-17 induced by MRSA infection. Furthermore, IL-17 blockade diminished the inflammation caused by MRSA. In vitro experiments demonstrated miR-155 positively regulated IL-17 expression and Th17 differentiation. Mechanistically, FOXP3 was a direct target of miR-155. miR-155 inhibited FOXP3 level via binding between FOXP3 and Argonaute 2 (AGO2), the key component of RNA-induced silencing complex (RISC). FOXP3 overexpression reversed elevated IL-17 levels and Th17 differentiation induced by miR-155. CONCLUSIONS: miR-155 facilitates Th17 differentiation by reducing FOXP3 through interaction of AGO2 and FOXP3 to promote the pathogenesis of MRSA pneumonia. IL-17 blockade weakens the inflammation due to MRSA, which provides a nonantibiotic treatment strategy for MRSA pneumonia.

Different Bacteria and their Antibiotic Sensitivity Patterns in Patients of Chronic Otitis Media-Active Mucosal Disease at a Secondary Care Centre in Delhi.

Chronic Otitis Media is characterized by distinct bacteriology compared with Acute Otitis Media, with COM being highly likely to harbor multiple bacteria of anaerobic and aerobic types of organisms (Cameron and Hussam K. El-Kashlan, xxx). In some patients, chronic infection with otorrhea will persist despite aggressive medical therapy. With the large number of cases of COM which presents to Sanjay Gandhi Memorial Hospital, and a majority being resistant to the common medications, we decided to undertake this study to have a better understanding of the bacterial epidemiology, the resistance, and what antibiotic to use in such cases. To determine the prevalence of different bacteriological agents and their antibiotic sensitivity pattern in patients of Chronic Otitis Media-Active Mucosal Disease presenting to ENT OPD at Sanjay Gandhi Memorial Hospital, Mangolpuri, Delhi. An observational cross-sectional study of 200 patients. After an initial examination, two sterile cotton swab sticks were introduced to collect pus samples from the medial part of the external auditory canal. The swabs were sent to the microbiology lab for Gram Staining, Culture, and Biochemical Tests, for identification of the different bacteriological agents and their antibiotic sensitivity patterns. Most common organism seen was Pseudomonas aeruginosa, followed by Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, mixed bacterial growth, and Candida spp. If regular monitoring of bacteriological profile is done in each hospital, this will help us to choose the antibiotics in a better manner and hence prevent the appearance of newer resistant strains.

One pot synthesis of 5-hydroxyalkylated thiadiazine thiones: Implication in pain management and bactericidal properties.

The synthesis of a new series of thiadiazine thiones including 5-(2-hydroxyethyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (1-5), 5-(2-hydroxypropyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (6-8), 3,5-dipropyl-1, 3, 5-thiadiazine-2-thione (9) and (2-(5-alkyl/aryl-6-thioxo-1, 3, 5-thiadiazine-3-yl) alkyl acetate/benzoate) (10-17) was accomplished via one pot reaction. The structures of the synthesized compounds were characterized through NMR and Mass spectrometry. The anti-nociceptive activity of compounds was performed on BALB/C mice by hot plate method, where compounds 3, 5 (50 µg/kg), and 8 (50, 100 µg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time of 15, 30, and 60 min, while compounds 6 and 16 (100 µg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time interval of 15 and 30 min. Compounds 1, 12-13, and 15 showed moderate activity. Among the tested hits, compounds 5 (17.3 ± 2.2), 11 (16.2 ± 2.1), and 8 (16.1 ± 2.1) showed significant anti-nociceptive potential. Molecular docking studies on the most active anti-nociceptive hits indicated that the activity might be attributed to the ability of the compounds to target µ-opioid receptor (µOR) effectively. Furthermore, compounds 14 and 11 showed anti-bacterial activity against Pseudomonas aeruginosa and MSRA with MIC of 40.97 and 54.77 µg/mL, respectively. In addition, the predicted ADMET profile of 5, 9, and 11 indicates that these molecules follow the drug-likeness criteria, and their activity can be enhanced through structural optimization.

Automated detection of methicillin-resistant Staphylococcus aureus with the MRSA CHROM imaging application on BD Kiestra Total Lab Automation System.

The virulence of methicillin-resistant Staphylococcus aureus (MRSA) and its potentially fatal outcome necessitate rapid and accurate detection of patients colonized with MRSA in healthcare settings. Using the BD Kiestra Total Lab Automation (TLA) System in conjunction with the MRSA Application (MRSA App), an imaging application that uses artificial intelligence to interpret colorimetric information (mauve-colored colonies) indicative of MRSA pathogen presence on CHROMagar chromogenic media, anterior nares specimens from three sites were evaluated for the presence of mauve-colored colonies. Results obtained with the MRSA App were compared to manual reading of agar plate images by proficient laboratory technologists. Of 1,593 specimens evaluated, 1,545 (96.98%) were concordant between MRSA App and laboratory technologist reading for the detection of MRSA growth [sensitivity 98.15% (95% CI, 96.03, 99.32) and specificity 96.69% (95% CI, 95.55, 97.60)]. This multi-site study is the first evaluation of the MRSA App in conjunction with the BD Kiestra TLA System. Using the MRSA App, our results showed 98.15% sensitivity and 96.69% specificity for the detection of MRSA from anterior nares specimens. The MRSA App, used in conjunction with laboratory automation, provides an opportunity to improve laboratory efficiency by reducing laboratory technologists' labor associated with the review and interpretation of cultures.

A case of community-acquired Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (MRSA) necrotizing pneumonia successfully treated with two anti-MRSA drugs.

A 22-year-old Vietnamese man was referred to our hospital owing to cough, dyspnea, and difficulty moving. The patient was diagnosed with community-acquired Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and necrotizing pneumonia. Treatment involved vancomycin (VCM) and meropenem, and the MRSA bacteremia improved. However, lung tissue destruction progressed. Therefore, linezolid was added to the VCM regimen, and this intervention led to the patient's recovery, and he was discharged from the hospital. Here, we report a case in which the patient was treated with a combination of two anti-MRSA drugs and was cured.

Comparison of efficacy and safety between daptomycin plus ß-lactam and daptomycin monotherapy for bloodstream infections due to gram-positive cocci: A systematic review and meta-analysis.

Objectives: We performed a comprehensive systematic review and meta-analysis to evaluate the clinical or microbiological outcomes and safety of a combination of daptomycin (DAP) and ß-lactams compared to DAP monotherapy in patients with blood stream infection (BSI) due to gram-positive cocci (GPC). Methods: We searched Scopus, PubMed, EMBASE, CINAHL, and Ityuushi databases up to January 30, 2023. Outcomes included all-cause mortality, clinical failure, and creatine phosphokinase (CPK) elevation. Results: Six cohorts or case-control studies fulfilled the inclusion criteria and were included in the final meta-analysis. Combination therapy of DAP and ß-lactams significantly reduced the mortality and clinical failure rate for all BSI due to GPC compared with the DAP monotherapy (mortality, odds ratio [OR] = 0.63, 95 % confidence interval [CI] = 0.41-0.98; clinical failure, OR = 0.42, 95 % CI = 0.22-0.81). In contrast, no significant difference was noted in the incidence of CPK elevation between the two groups (OR = 0.85, 95 % CI = 0.39-1.84). Conclusion: Altogether, combination therapy of DAP and ß-lactams can improve the prognosis for patients with BSI due to GPC compared with DAP alone. Therefore, it should be considered as an option for the empirical treatment of BSI caused by GPC.

In Vitro Antimicrobial Photodynamic Therapy for Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) Inhibition Using a Green Light Source.

Photodynamic therapy (PDT) has been based on using photosensitizers (PS) and applying light of a specific wavelength. When this technique is used for treating infections, it is known as antimicrobial photodynamic therapy (aPDT). Currently, the use of lighting sources for in vitro studies using aPDT is generally applied in multiwell cell culture plates; however, depending on the lighting arrangement, there are usually errors in the application of the technique because the light from a well can affect the neighboring wells or it may be that not all the wells are used in the same experiment. In addition, one must be awarded high irradiance values, which can cause unwanted photothermal problems in the studies. Thus, this manuscript presents an in vitro antimicrobial photodynamic therapy for a Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) inhibition study using an arrangement of thermally isolated and independently illuminated green light source systems for eight tubes in vitro aPDT, determining the effect of the following factors: (i) irradiance level, (ii) exposure time, and (iii) Rose Bengal (RB) concentration (used as a PS), registering the Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) inhibition rates. The results show that in the dark, RB had a poor antimicrobial rate for P. aeruginosa, finding the maximum inhibition (2.7%) at 30 min with an RB concentration of 3 µg/mL. However, by applying light in a correct dosage (time × irradiance) and the adequate RB concentration, the inhibition rate increased by over 37%. In the case of MRSA, there was no significant inhibition with RB in complete darkness and, in contrast, the rate was 100% for those experiments that were irradiated.

Native Aortic Valve Infective Endocarditis Secondary to Community-Acquired Methicillin-Resistant Staphylococcus aureus: A Case Report and Literature Review.

Infective endocarditis (IE) refers to a microbial infection affecting either a heart valve or endocardium, resulting in tissue damage and the formation of vegetation. Native aortic valve endocarditis in children is rare and is associated with serious complications related to valvular insufficiency and systemic embolizations. As reports about community-acquired methicillin-resistant Staphylococcus aureus (MRSA) native aortic valve endocarditis in children are very scarce, we report this case along with a literature review about its complications and management. Here, we report the case of a seven-month-old infant who was previously healthy and presented with signs and symptoms of shock and systemic embolizations secondary to native aortic valve IE. His blood culture showed MRSA. He developed aortic valve insufficiency heart failure and multiorgan septic emboli that progressed to fatal refractory multiorgan failure. The management of complicated aortic valve endocarditis in children is challenging and needs a multidisciplinary team approach and prompt intervention.

Assessing the discriminability of PCR-based open reading frame typing versus single-nucleotide polymorphism analysis via draft whole-genome sequencing of methicillin-resistant Staphylococcus aureus in nosocomial transmission analysis.

Phylogenetic analysis based on single-nucleotide polymorphism (SNP)-based through whole-genome sequencing is recognized as the standard method for probing nosocomial transmission. However, the application of WGS is constrained by the high cost of equipment and the need for diverse analysis tools, which limits its widespread use in clinical laboratory settings. In Japan, the prevalent use of PCR-based open reading frame typing (POT) for tracing methicillin-resistant Staphylococcus aureus (MRSA) transmission routes is attributed to its simplicity and ease of use. Although POT's discriminatory power is considered insufficient for nosocomial transmission analysis, conclusive data supporting this notion is lacking. This study assessed the discriminatory capabilities of SNP analysis and POT across 64 clinical MRSA strains. All 21 MRSA strains of ST5/SCCmec IIa, having more than 16 SNPs, demonstrated distinct clones. Conversely, two strains shared the same POT number and were identified as group A. Among the 12 MRSA strains of ST8/SCCmec IVl with over nine SNPs, five fell into POT group B, and five into POT group C. All four MRSA strains of ST8/SCCmec IVa were classified into POT group D, although they included strains with more than 30 SNPs. Among the 27 MRSA strains of ST1/SCCmec IVa, 14 were classified into POT group E. However, except for two clusters (each comprising two or three strains), all had SNP counts >10 (Fig. 1-D). SNP analysis of MRSA in CC1/SCCmec IV showed that several strains had the same number of SNPs in POT number (106-183-37), even among bacteria with >100 SNPs, indicating POT's limited use in detailed nosocomial transmission analysis.

Simultaneous Dual-Gene Test of Methicillin-Resistant Staphylococcus Aureus using an Argonaute-Centered Portable and Visual Biosensor.

The development of novel method for drug-resistant bacteria detection is imperative. A simultaneous dual-gene Test of methicillin-resistant Staphylococcus aureus (MRSA) is developed using an Argonaute-centered portable biosensor (STAR). This is the first report concerning Argonaute-based pathogenic bacteria detection. Simply, the species-specific mecA and nuc gene are isothermally amplified using loop-mediated isothermal amplification (LAMP) technique, followed by Argonaute-based detection enabled by its programmable, guided, sequence-specific recognition and cleavage. With the strategy, the targeted nucleic acid signals gene are dexterously converted into fluorescent signals. STAR is capable of detecting the nuc gene and mecA gene simultaneously in a single reaction. The limit of detection is 10 CFU/mL with a dynamic range from 10 to 107 CFU/mL. The sample-to-result time is <65 min. This method is successfully adapted to detect clinical samples, contaminated foods, and MRSA-infected animals. This work broadens the reach of Argonaute-based biosensing and presents a novel bacterial point-of-need (PON) detection platform.

High prevalence of ST5-SCCmec II-t311 clone of methicillin-resistant Staphylococcus aureus isolated from bloodstream infections in East China.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is a challenging global health threat, resulting in significant morbidity and mortality worldwide. This study aims to determine the molecular characteristics and antimicrobial susceptibility of 263 MRSA isolates in Zhejiang Province, east China. METHODS: From 2014 to 2019, a total of 263 MRSA isolates from bloodstream infections (BSIs) were collected from 6 hospitals in 4 cities in Zhejiang province, east China. Antimicrobial susceptibility tests were conducted according to the guidelines set forth by the Clinical and Laboratory Standards Institute (CLSI). To characterize and analyze these isolates, multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing and virulence genes gene profiles were performed. RESULTS: The most predominant clone was ST5-SCCmec II-t311, which accounted for 41.8% (110/263), followed by ST59 (44/263, 16.7%). Compared with non-ST5-II-t311 isolates, ST5-II-t311 isolates were more resistant to erythromycin, tetracycline, levofloxacin, moxifloxacin, and ciprofloxacin, but more susceptible to clindamycin. Moreover, the rates of multidrug resistance were higher in ST5-II-t311 isolates compared to the non-ST5-II-t311 isolates. In comparison to the non-ST5-II-t311 isolates, ST5-II-t311 isolates showed no significant difference in virulence genes detected. CONCLUSIONS: MRSA ST5-II-t311 clone has become the most predominant clone in Zhejiang Province, east China and has higher rates of multidrug resistance than other isolates, that should be kept in mind when treating BSI. Moreover, MRSA ST59 clone shows an upward trend and has begun to spread into hospitals. Our findings highlight the importance of epidemiological studies of S. aureus carriage in the eastern region.

Clinical impact and public health challenges of a PVL-MRSA bacteraemia outbreak amongst people who inject drugs in South Yorkshire, UK.

Background: Panton-Valentine leukocidin (PVL) Staphylococcus aureus (SA) is an emergent public health concern. PVL toxin has been mostly associated with methicillin-sensitive S. aureus (MSSA)-related skin and soft tissue infections occurring in high-risk groups such as people who inject drugs (PWID). The emergence of PVL methicillin-resistant S. aureus (MRSA) infection is causing severe and life-threatening disease in PWID. Clinical cases: We present an outbreak of eight PVL-MRSA bacteraemia cases at a UK teaching hospital between 2018 and 2022. An additional four patients developed bacteraemia with PVL-negative MRSA of the same multilocus sequence type (MLST). All patients were PWID and aged 33-51 years old. Four patients developed MRSA bacterial endocarditis. Three patients died. These cases represent the initial cases detected at Doncaster and Bassetlaw Teaching Hospitals of what is an ongoing and developing outbreak. Management: An outbreak investigation has been undertaken in association with the UK Health Security Agency. Epidemiological factors have been explored, including via direct contact at a local sheltered accommodation and the possibility of a contaminated drug supply. Whole-genome sequencing confirmed that all isolates were closely related and of the same MLST (sequence type 5). A community substance misuse group disseminated health education on the prevention of PVL-MRSA. Preventing infection in PWID presents a major challenge due to the impact of addiction on engagement with services and the significant barriers faced by our patients in observing infection prevention measures. Conclusion: PVL-MRSA is of major public health concern and outbreak investigation and mapping out local epidemiological patterns plays a vital role in preventing further spread throughout the community. Additionally, this work enables targeted and early treatment in patients in high-risk categories for disease. These cases of PVL-MRSA infection in PWID highlights the transmissibility, pathogenic potential and severe clinical disease spectrum within this population. Further work is required to tackle transmission and infection from this pathogenic strain.