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Clonal complex 398 (CC398) methicillin-resistant Staphylococcus aureus (MRSA) is a new rising threat of community-associated (CA) MRSA infection in humans.
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Panton-Valentine-leukocidin-positive ST1232-V MRSA is a noteworthy CA CC398 MRSA strain.
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Children, as well as adults, are also at risk of CA CC398 MRSA infection.
Abstract
Invasive community-associated methicillin-resistant Staphylococcus aureus (MRSA) diseases caused by clonal complex 398 MRSA without animal contact have become a new emerging threat. We report a case of bacteremic mediastinitis caused by a Panton-Valentine leukocidin-positive community-associated sequence type 1232 MRSA in a Taiwanese baby aged 4 months without animal contact.
Community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) has prevailed worldwide for at least two decades, which is disproportionate in the pediatric population [
]. In addition to major CA-MRSA clones worldwide, the threat from another category of MRSA, clonal complex (CC) type 398, is surging. One CC398 MRSA clone, which is associated with livestock-associated (LA) MRSA-related infections among adults over the years, contributes to the disease spectrum from skin and soft tissue infections (SSTIs) to fatal invasive diseases [
]. Whole genome sequencing (WGS) and a phylogenetic analysis-disclosed CC398 MRSA can be divided into LA and human-adapted (HA) clone. CC398 HA-MRSA belonged to the II-GOI clade and was genetically close to a common lineage of Southeast Asia [
]. CC398 HA-MRSA is featured with frequent loss of antimicrobial resistance genes, acquisition of β-converting ϕ3-prophage variants and immune evasion genes, and biofilm formation, which promote its adaptation and invasiveness [
]. CC398 HA-MRSA comprises three noteworthy variants: the Panton-Valentine leukocidin (PVL)-positive ST398-V, ST398 single variant ST1232-V, and PVL-negative ST-398 V clones [
], ST398 HA-MRSA infections were increasingly identified in Europe and Australia, and many infected individuals have a travel history from Southeast Asia, and those isolates strains shared many genetic characteristics with strains from China [
]. Based on the mounting epidemiological evidence, this CC398 HA-MRSA clone now is regarded as a cause of CA-MRSA.
Despite mounting adult cases, CC398 MRSA infections are barely reported in children. Herein, we report an invasive MRSA infection caused by PVL-positive CC398 MRSA (ST1232 strain) in a small baby without animal contact.
Case report
A full-term and well nurtured male baby aged 4 months was admitted in our hospital in early March 2022. He lives in a big urban city and is cared for by his grandparents. Over the previous 72 hours, he had been presenting with a persistently spiking fever without focus. Before admission, he had been checked by two general pediatricians and acute pharyngitis was ascertained but no recognizable symptoms—such as cough, rhinorrhea, vomiting, diarrhea, and skin rash—emerged. His caregivers noticed a progressive drop in his oral intake and activity; therefore, he was sent to our hospital for further evaluation.
Upon admission, he was febrile with a body temperature above 39°C. The patient appeared ill and not doing well. He had a pulse rate of 168 beats/minute, respiratory rate of 60 cycles/minute, and blood pressure of 87/40 mm Hg. Physical examination showed no injected throat, no bulging fontanelle, and no palpable neck mass or lymph nodes but had labored breathings with bilateral coarse breath sounds. Initial laboratory tests showed leukocytosis (white blood cell 24,620/µl, segmented 44%, lymphocytes 43%, band 4%, platelet 491,000/µl, and hemoglobin 12.1 g/dl). The C-reactive protein (normal limit: <0.5 mg/dl) was 25.52 mg/dl. His SARS-CoV-2 reverse transcriptase-polymerase chain reaction was negative, urine was clean, urine pneumococcal antigen test was negative, and cerebrospinal fluid was totally sterile. Unexpectedly, a widened mediastinum and cardiomegaly were revealed by chest X-ray (Figure 1a), and an abscess or mass-like lesion over the anterior mediastinum area with pericardial effusion was found by chest sonography. We started with a broad-spectrum antimicrobial therapy with cefotaxime and gentamicin, which were switched to teicoplanin and ceftaroline in combination, upon detecting the growth of gram-positive cocci from two sets of blood cultures within 12 hours.
Figure 1Chest image studies of this patient and whole genome sequence phylogenetic analysis of the isolated MRSA strain.
(a) Chest X-ray obtained upon admission disclosed a widen mediastinum and cardiomegaly. (b) Chest computed tomography scan showed multi-lobulated abscess formation in the anterior mediastinum. (c) Whole genome sequencing phylogenetic analysis indicates that this MRSA isolate (CBSH1110135) is an HA Panton-Valentine-leukocidin-positive ST1232 MRSA and genetically close to the ST1232 MRSA strains in Australia.
On day 3 of hospitalization, a chest computed tomography scan showed an abscess accumulated in the anterior mediastinum and pericardial area, along with bilateral pneumonia and pleural effusion (Figure 1b). The child received video-assisted thoracoscopic surgery intervention on day 5. There were two blood cultures and one pleural pus culture growing MRSA, which was resistant to clindamycin and erythromycin but sensitive to trimethoprim/sulfamethoxazole, doxycycline, vancomycin, teicoplanin, and daptomycin. He was intermittently febrile during the first 7 hospital days and scattered reddish skin rashes erupted transiently on his trunk for 2 days but there was no hypotension or shock. Blood cultures obtained on day 5 and 7 were all sterile. Cardiac evaluation was completely normal, and no vegetation or tamponade was found. He was afebrile since day 8 and the C-reactive protein level turned to normal on day 11. In total, he received 10 days of ceftaroline and 21 days of teicoplanin therapy, and he recovered uneventfully.
The genomic DNA of this MRSA strain cannot be digested by SmaI, and molecular analysis characterized this MRSA isolate as PVL-positive, SCCmec type V, and ST1232 MRSA (a single locus variant of ST398 MRSA). Advanced WGS and phylogenetic analysis of core genome indicated that this MRSA isolate is an HA strain, clustered into PVL-positive II-GOI (group of interest) clade, and phylogenetically related to human MRSA strains identified in Australia.
Discussion
In the era of CA-MRSA for more than two decades, invasive MRSA disease in the pediatric group has been common [
]. In children, SSTIs are the most common clinical manifestation, but several invasive diseases, such as bloodstream infection, osteomyelitis, and infective endocarditis, have been reported [
CC398 MRSA was first identified in the early 2000s LA-MRSA-related infection CC398, which is widespread in pig farms and farm workers in Europe. In humans, CC398 MRSA is not the dominant MRSA clone accounting for clinical infection; however, a growing number of individuals infected with CC398 MRSA had no connection with livestock was reported over the past 10 years. CC398 MRSA has been reported to account for 16% and 21% of all MRSA bloodstream infections and SSTIs in Demark in 2016 [
Sequence types 8, 59, and 45 methicillin resistant Staphylococcus aureus as the predominant strains causing skin and soft tissue infections in Taiwan's prisons and jails.
]. WGS analysis indicated this PVL-positive ST1232-V MRSA strain is positioned in the HA II-GOI clade and genetically close to the Australia ST1232 MRSA strains. This finding is in line with the reports from Japan and Australia [
Necrotizing mediastinitis is an unusual but critical illness, which is commonly caused by a descending oropharyngeal or neck infection. Early recognition is crucial to prevent disease progress and potential airway emergency. The typical manifestation of necrotizing mediastinitis includes fever, odynophagia, cervical swelling, cervical pain, and dyspnea [
]. A computed tomography scan is mandatory to make an early diagnosis, and aggressive surgical intervention and appropriate antimicrobial therapy are keystones for treatment success [
]. In our case, the patient did not present these aforementioned symptoms, except for fever. The reports of the invasiveness of ST 1232 MRSA infection are limited, ranging from SSTIs to invasive arthritis, thoracic empyema, and endocarditis [
]. Because ST 1232 MRSA carries SCCmec V, it was reported to be resistant to erythromycin, tetracycline, clindamycin, and gentamicin but sensitive to all anti-MRSA agents [
]. Timely diagnosis and prompt treatment are key for his successful outcome. However, it is hard to answer how he contracted the MRSA infection. Presumably, because the child had no contact with livestock, a person-to-person transmission may be the cause, which in turn brings us to speculate this ST1232 MRSA clone has successfully adapted in human population in Taiwan.
In conclusion, we have presented an invasive disease caused by CA CC398 MRSA in a healthy child as young as 4 months. Clinicians need to have a high index of suspicion for invasive CA-MRSA infection in this setting: a febrile baby with widened mediastinum and critical illness. In addition, this case highlights that PVL-positive ST1232-V MRSA clone is appearing in our community and poses a potential threat to all populations regardless of age. It is noteworthy to monitor the spreading and evolving trend of this MRSA strain in the future.
Declaration of competing interest
The authors have no competing interests to declare.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Consent
Written informed consent was obtained from patient's parents.
Author contributions
Chun Yi Lee: patient care, data presenting, and manscript writing. Chih Jung Chen: bacterial whole genome sequencing and phylogenetic analysis.
Sequence types 8, 59, and 45 methicillin resistant Staphylococcus aureus as the predominant strains causing skin and soft tissue infections in Taiwan's prisons and jails.
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