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Che Hamzah AM, Chew CH, Al-Trad EI, Puah SM, Chua KH, A Rahman NI, Ismail S, Maeda T, Palittapongarnpim P, Yeo CC. Whole genome sequencing of methicillin-resistant Staphylococcus aureus clinical isolates from Terengganu, Malaysia, indicates the predominance of the EMRSA-15 (ST22-SCCmec IV) clone. Sci Rep 2024; 14:3485. [PMID: 38347106 PMCID: PMC10861583 DOI: 10.1038/s41598-024-54182-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Accepted: 02/09/2024] [Indexed: 02/15/2024] Open
Abstract
Despite the importance of methicillin-resistant Staphylococcus aureus (MRSA) as a priority nosocomial pathogen, the genome sequences of Malaysian MRSA isolates are currently limited to a small pool of samples. Here, we present the genome sequence analyses of 88 clinical MRSA isolates obtained from the main tertiary hospital in Terengganu, Malaysia in 2016-2020, to obtain in-depth insights into their characteristics. The EMRSA-15 (ST22-SCCmec IV) clone of the clonal complex 22 (CC22) lineage was predominant with a total of 61 (69.3%) isolates. Earlier reports from other Malaysian hospitals indicated the predominance of the ST239 clone, but only two (2.3%) isolates were identified in this study. Two Indian-origin clones, the Bengal Bay clone ST772-SCCmec V (n = 2) and ST672 (n = 10) were also detected, with most of the ST672 isolates obtained in 2020 (n = 7). Two new STs were found, with one isolate each, and were designated ST7879 and ST7883. From the core genome phylogenetic tree, the HSNZ MRSA isolates could be grouped into seven clades. Antimicrobial phenotype-genotype concordance was high (> 95%), indicating the accuracy of WGS in predicting most resistances. Majority of the MRSA isolates were found to harbor more than 10 virulence genes, demonstrating their pathogenic nature.
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Affiliation(s)
- Ainal Mardziah Che Hamzah
- Faculty of Health Sciences, Universiti Sultan Zainal Abidin, 21300, Kuala Nerus, Terengganu, Malaysia
| | - Ching Hoong Chew
- Faculty of Health Sciences, Universiti Sultan Zainal Abidin, 21300, Kuala Nerus, Terengganu, Malaysia.
| | - Esra'a Ibrahim Al-Trad
- Centre for Research in Infectious Diseases and Biotechnology (CeRIDB), Faculty of Medicine, Universiti Sultan Zainal Abidin, 20400, Kuala Terengganu, Terengganu, Malaysia
- Faculty of Allied Medical Sciences, Jadara University, Irbid, Jordan
| | - Suat Moi Puah
- Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Kek Heng Chua
- Department of Biomedical Science, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Nor Iza A Rahman
- Centre for Research in Infectious Diseases and Biotechnology (CeRIDB), Faculty of Medicine, Universiti Sultan Zainal Abidin, 20400, Kuala Terengganu, Terengganu, Malaysia
| | - Salwani Ismail
- Centre for Research in Infectious Diseases and Biotechnology (CeRIDB), Faculty of Medicine, Universiti Sultan Zainal Abidin, 20400, Kuala Terengganu, Terengganu, Malaysia
| | - Toshinari Maeda
- Department of Biological Functions and Engineering, Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, 2-4 Hibikino, Wakamatsu-Ku, Kitakyushu, 808-0196, Japan
| | - Prasit Palittapongarnpim
- Pornchai Matangkasombut Center for Microbial Genomics (CENMIG), Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
| | - Chew Chieng Yeo
- Centre for Research in Infectious Diseases and Biotechnology (CeRIDB), Faculty of Medicine, Universiti Sultan Zainal Abidin, 20400, Kuala Terengganu, Terengganu, Malaysia.
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Hofstee MI, Siverino C, Saito M, Meghwani H, Tapia-Dean J, Arveladze S, Hildebrand M, Rangel-Moreno J, Riool M, Zeiter S, Zaat SAJ, Moriarty TF, Muthukrishnan G. Staphylococcus aureus Panton-Valentine Leukocidin worsens acute implant-associated osteomyelitis in humanized BRGSF mice. JBMR Plus 2024; 8:ziad005. [PMID: 38505530 PMCID: PMC10945728 DOI: 10.1093/jbmrpl/ziad005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/21/2024] Open
Abstract
Staphylococcus aureus is the most common pathogen that causes implant-associated osteomyelitis, a clinically incurable disease. Immune evasion of S. aureus relies on various mechanisms to survive within the bone niche, including the secretion of leukotoxins such as Panton-Valentine leukocidin (PVL). PVL is a pore-forming toxin exhibiting selective human tropism for C5a receptors (C5aR1 and C5aR2) and CD45 on neutrophils, monocytes, and macrophages. PVL is an important virulence determinant in lung, skin and soft tissue infections. The involvement of PVL in S. aureus pathogenesis during bone infections has not been studied extensively yet. To investigate this, humanized BALB/c Rag2-/-Il2rg-/-SirpaNODFlk2-/- (huBRGSF) mice were subjected to transtibial implant-associated osteomyelitis with community-acquired methicillin-resistant S. aureus (CA-MRSA) USA300 wild type strain (WT), an isogenic mutant lacking lukF/S-PV (Δpvl), or complemented mutant (Δpvl+pvl). Three days post-surgery, Δpvl-infected huBRGSF mice had a less severe infection compared to WT-infected animals as characterized by 1) improved clinical outcomes, 2) lower ex vivo bacterial bone burden, 3) absence of staphylococcal abscess communities (SACs) in their bone marrow, and 4) compromised MRSA dissemination to internal organs (liver, kidney, spleen, heart). Interestingly, Δpvl-infected huBRGSF mice had fewer human myeloid cells, neutrophils, and HLA-DR+ monocytes in the bone niche compared to WT-infected animals. Expectedly, a smaller fraction of human myeloid cells were apoptotic in the Δpvl-infected huBRGSF animals. Taken together, our study highlights the pivotal role of PVL during acute implant-associated osteomyelitis in humanized mice.
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Affiliation(s)
- Marloes I Hofstee
- AO Research Institute Davos, 7270 Davos, Switzerland
- Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Amsterdam institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | | | - Motoo Saito
- Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, United States
- Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, NY 14618, United States
| | - Himanshu Meghwani
- Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, United States
- Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, NY 14618, United States
| | | | | | | | - Javier Rangel-Moreno
- Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14620, United States
| | - Martijn Riool
- Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Amsterdam institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
- Department of Trauma Surgery, University Hospital Regensburg, 93053 Regensburg, Germany
| | | | - Sebastian A J Zaat
- Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Amsterdam institute for Infection and Immunity, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | | | - Gowrishankar Muthukrishnan
- Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, United States
- Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, NY 14618, United States
- Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, United States
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Cuddihy J, Patel S, Mughal N, Lockie C, Trimlett R, Ledot S, Cheshire N, Desai A, Singh S. Near-fatal Panton-Valentine leukocidin-positive Staphylococcus aureus pneumonia, shock and complicated extracorporeal membrane oxygenation cannulation: A case report. World J Crit Care Med 2021; 10:301-309. [PMID: 34616664 PMCID: PMC8462017 DOI: 10.5492/wjccm.v10.i5.301] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 06/17/2021] [Accepted: 08/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Panton-Valentine leukocidin (PVL) is an exotoxin secreted by Staphylococcus aureus (S. aureus), responsible for skin and soft tissue infections. As a cause of severe necrotising pneumonia, it is associated with a high mortality rate. A rare entity, the epidemiology of PVL S. aureus (PVL-SA) pneumonia as a complication of influenza coinfection, particularly in young adults, is incompletely understood.
CASE SUMMARY An adolescent girl presented with haemoptysis and respiratory distress, deteriorated rapidly, with acute respiratory distress syndrome (ARDS) and profound shock requiring extensive, prolonged resuscitation, emergency critical care and venovenous extracorporeal membrane oxygenation (ECMO). Cardiac arrest and a rare complication of ECMO cannulation necessitated intra-procedure extracorporeal cardiopulmonary resuscitation, i.e., venoarterial ECMO. Coordinated infectious disease, microbiology and Public Health England engagement identified causative agents as PVL-SA and influenza A/H3N2 from bronchial aspirates within hours. Despite further complications of critical illness, the patient made an excellent recovery with normal cognitive function. The coordinated approach of numerous multidisciplinary specialists, nursing staff, infection control, specialist cardiorespiratory support, hospital services, both adult and paediatric and Public Health are testimony to what can be achieved to save life against expectation, against the odds. The case serves as a reminder of the deadly nature of PVL-SA when associated with influenza and describes a rare complication of ECMO cannulation.
CONCLUSION PVL-SA can cause severe ARDS and profound shock, with influenza infection. A timely coordinated multispecialty approach can be lifesaving.
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Affiliation(s)
- Joshua Cuddihy
- Magill Department for Anaesthesia, Critical Care and Pain Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London SW10 9NH, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London SW7 2BU, United Kingdom
| | - Shreena Patel
- Chelsea and Westminster Hospital, Chelsea and Westminster Hospital NHS Foundation Trust, London SW10 9NH, United Kingdom
- Warwick Medical School, Warwick University, Warwick CV4 7HL, United Kingdom
| | - Nabeela Mughal
- Microbiology and Infectious Diseases, Chelsea and Westminster Hospital NHS Foundation Trust, London SW10 9NH, United Kingdom
- Imperial College London, Imperial College London, London SW7 2BU, United Kingdom
| | - Christopher Lockie
- Intensive Care Unit, Chelsea and Westminster Hospital NHS Foundation Trust, London SW10 9NH, United Kingdom
| | - Richard Trimlett
- Cardiac Surgery, Royal Brompton and Harefield NHS Foundation Trust, London SW3 6NP, United Kingdom
| | - Stephane Ledot
- Adult Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London SW3 6NP, United Kingdom
| | - Nicholas Cheshire
- Vascular Surgery, Royal Brompton and Harefield NHS Foundation Trust, London SW3 6NP, United Kingdom
| | - Ajay Desai
- Paediatric Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London SW3 6NP, United Kingdom
| | - Suveer Singh
- Imperial College London, Imperial College London, London SW7 2BU, United Kingdom
- Adult Intensive Care Unit, Royal Brompton and Harefield NHS Foundation Trust, London SW3 6NP, United Kingdom
- Department of Intensive Care Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom
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Pichon M, Micaelo M, Rasoanandrasana S, Menn AM. Molecular characterization of Staphylococcus aureus isolates derived from severe pneumonia: a retrospective monocentre study. Infect Dis (Lond) 2021; 53:811-819. [PMID: 34382901 DOI: 10.1080/23744235.2021.1963472] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Staphylococcus aureus is endowed with a repertoire of virulence factors potentially implicated in its pathogenicity and ability to cause invasive disease. The main objective of this study was to describe the bacterial genotype, including virulence genes and affiliation to clonal complexes (CCs), encountered in severe pneumonia. METHODS DNA microarray was used to analyse 18 S. aureus isolates from patients hospitalized with severe pneumonia between 2017 and 2019. RESULTS Among 18 S. aureus isolates, 14 were methicillin-susceptible S. aureus (MSSA), and 4 methicillin-resistant S. aureus (MRSA). There were 14 community-acquired, 3 healthcare-associated, and 1 hospital-acquired infections. Different radiological presentations were observed: necrotizing pneumonia (n = 8, 44%), alveolar consolidation (n = 7, 39%), alveolar-interstitial infiltrates (n = 3, 17%). Sixteen patients (89%) required ICU hospitalization, 13 (72%) an invasive mechanical ventilation, and 12 (67%) a vasopressor support. Mortality affected 6 patients (33%). Panton-Valentine leukocidin (PVL), staphylococcal enterotoxins, toxic shock syndrome toxine-1 (TSST-1) encoding genes were documented in nine (50%), 12 (67%), one (6%) of the isolates, respectively. Accessory regulator gene group I was the most reported (n = 9, 50%) and was found in five deaths. The majority of isolates were affiliated to CC152 (n = 6), followed by CC15 (n = 3), CC45 (n = 2), CC30 (n = 2), CC1 (n = 2), CC8 (n = 1), CC9 (n = 1), and CC25 (n = 1). All the CC152 isolates were PVL-positive. CONCLUSION CC152-PVL positive S. aureus strains were the most prevalent in severe pneumonia. Other virulence gene profiles were found coupled to additional clonal lineages. A genotyping strategy contributes to describe the current circulating strains and bacterial genetic backgrounds.
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Affiliation(s)
- Maud Pichon
- Service de Médecine Polyvalente, Centre Hospitalier Victor Dupouy, Argenteuil, France
| | - Maïte Micaelo
- Service de Microbiologie, Centre Hospitalier Victor Dupouy, Argenteuil, France
| | | | - Anne-Marie Menn
- Service de Médecine Polyvalente, Centre Hospitalier Victor Dupouy, Argenteuil, France
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Castellazzi ML, Bosis S, Borzani I, Tagliabue C, Pinzani R, Marchisio P, di Pietro GM. Panton-valentine leukocidin Staphylococcus aureus severe infection in an infant: a case report and a review of the literature. Ital J Pediatr 2021; 47:158. [PMID: 34274022 PMCID: PMC8285845 DOI: 10.1186/s13052-021-01105-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/08/2021] [Indexed: 01/05/2023] Open
Abstract
Background Panton-Valentine leukocidin (PVL) is one of the major virulence factor of Staphylococcus aureus (SA) that might be associated with invasive life-threating infections. A prompt diagnosis and adequate treatment are essential in achieving the best outcome and avoiding serious sequelae. We describe a case of severe invasive PVL-SA infection in an infant. A literature review starting from 2010 was also performed in order to discuss clinical presentations, radiological findings, treatment and outcome. Case presentation This is a case of a 6-month-old boy who rapidly developed high fever and poor general condition. He was diagnosed as having multiple muscular abscesses, multiple foci of osteomyelitis and bloodstream infections caused by Panton-Valentine leukocidin Methicillin-resistant Staphylococcus aureus. He received intravenous antibiotics and surgical drainage of the abscess with progressive recovery. Conclusion Our report highlights the importance of improving awareness of this severe infection, as a prompt diagnosis and adequate manage is essential in order to save life and to prevent serious complications.
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Affiliation(s)
- Massimo Luca Castellazzi
- Paediatric Emergency Department, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Samantha Bosis
- Paediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Irene Borzani
- Radiology Unit - Paediatric Division, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Claudia Tagliabue
- Paediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Raffaella Pinzani
- Paediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Paola Marchisio
- Paediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Chenouf NS, Mama OM, Messaï CR, Ruiz-Ripa L, Fernández-Fernández R, Carvalho I, Zitouni A, Hakem A, Torres C. Detection of methicillin-resistant coagulase-negative staphylococci and PVL/mecA genes in cefoxitin-susceptible Staphylococcus aureus (t044/ST80) from unpasteurized milk sold in stores in Djelfa, Algeria. J Dairy Sci 2021; 104:2684-2692. [PMID: 33455787 DOI: 10.3168/jds.2020-19270] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 11/10/2020] [Indexed: 02/04/2023]
Abstract
This study was designed to determine antimicrobial resistance phenotypes and genotypes and virulence factors in Staphylococcus aureus and coagulase-negative staphylococci (CNS) in unpasteurized milk sold in Djelfa, Algeria. Eighty-two unpasteurized cow milk samples were randomly obtained from 82 retail stores in Djelfa and tested to detect staphylococci. Species were identified by biochemical tests and MALDI-TOF. Antimicrobial resistance phenotypes and genotypes were determined by disk diffusion test, PCR, and sequencing. The Staph. aureus isolates were subjected to spa typing, multilocus sequence typing, and detection of virulence genes and the scn gene by PCR and sequencing. Forty-five (54.9%) milk samples were contaminated by staphylococci and 45 isolates were recovered: 10 Staph. aureus (12.2% of total samples) and 35 CNS (42.7%). Resistance to penicillin (blaZ), tetracycline (tetL/tetK), and erythromycin (ermB/msrA/ermC) were the most common phenotypes (genotypes). Three CNS were methicillin-resistant and all were mecA-positive. The Staph. aureus isolates were ascribed to the following lineages [spa type/sequence type/associated clonal complex (number of isolates)]: t267/ST479/CC479 (n = 6), t1510/ST5651/CC45 (n = 1), t359/ST97/CC97/ (n = 1), t346/ST15/CC15 (n = 1), and t044/ST80 (n = 1). The mecA gene was detected in the cefoxitin-susceptible t044/ST80 isolate and co-harbored the lukF/lukS-PV and scn genes. The detection of mecA-PVL-positive Staph. aureus, methicillin-resistant CNS, and multidrug-resistant staphylococcal species indicates a potentially serious health issue and reveals that unpasteurized milk sold in Djelfa city could be a potential vehicle for pathogenic and antimicrobial-resistant staphylococci.
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Affiliation(s)
- Nadia Safia Chenouf
- Laboratoire d'Exploration et de Valorisation des Ecosystèmes Steppiques, BP3117, University of Djelfa, 17000 Algeria; Faculté des Sciences de la Nature et de la Vie, BP3117, University of Djelfa, 17000 Algeria; Laboratoire de Biologie des Systèmes Microbiens (LBSM), BP92, 16050, Ecole Normale Supérieure de Kouba, Algiers, Algeria; Area Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, 26006 Logroño, Spain
| | - Olouwafemi Mistourah Mama
- Area Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, 26006 Logroño, Spain
| | - Chafik Redha Messaï
- Laboratoire de Santé et Productions Animales, Rue Issad Abbes, Oued Smar 16000, Ecole Supérieure Nationale Vétérinaire, Algiers, Algeria
| | - Laura Ruiz-Ripa
- Area Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, 26006 Logroño, Spain
| | - Rosa Fernández-Fernández
- Area Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, 26006 Logroño, Spain
| | - Isabel Carvalho
- Area Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, 26006 Logroño, Spain; University of Trás-os-Montes e Alto Douro (UTAD), 5000 Vila Real, Portugal
| | - Abdelghani Zitouni
- Laboratoire de Biologie des Systèmes Microbiens (LBSM), BP92, 16050, Ecole Normale Supérieure de Kouba, Algiers, Algeria
| | - Ahcène Hakem
- Laboratoire d'Exploration et de Valorisation des Ecosystèmes Steppiques, BP3117, University of Djelfa, 17000 Algeria; Center of Research in Agropastoralism, Djelfa, 17000, Algeria
| | - Carmen Torres
- Area Bioquímica y Biología Molecular, Universidad de La Rioja, Madre de Dios 51, 26006 Logroño, Spain.
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7
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Retrospective study of pneumonia due to Panton-Valentine leukocidin-producing Staphylococcus aureus in Reunion. Med Mal Infect 2019; 49:534-539. [PMID: 30765285 DOI: 10.1016/j.medmal.2019.01.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 04/19/2018] [Accepted: 01/23/2019] [Indexed: 11/20/2022]
Abstract
OBJECTIVE Panton-Valentine leukocidin-producing Staphylococcus aureus necrotizing pneumonia is an unusual cause of community-acquired pneumonia, although associated with a high case fatality. This infection mainly affects young individuals, without any history, and is most often preceded by flu-like symptoms. METHOD We focused on patients presenting with Staphylococcus aureus necrotizing pneumonia in Reunion (Indian Ocean) admitted to the emergency department. We performed a retrospective study based on data collected from laboratory registers and medical files of patients presenting with Staphylococcus aureus necrotizing pneumonia in Reunion between December 2014 and December 2017. RESULTS A total of 16 patients were recruited for this study, with a median age of 40.5 years. More than half of patients had previously been admitted to the emergency department for acute respiratory distress syndrome or severe sepsis. Fourteen patients were admitted to the intensive care unit and six patients died (five premature deaths). CONCLUSION Physicians should be aware of this infection during the flu season and quickly adapt the specific antibiotic treatment, including a drug inhibiting toxin production. As methicillin-resistant Staphylococcus aureus is very rarely observed in Reunion, physicians can still adapt the empirical treatment, without glycopeptides.
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Kemung HM, Tan LTH, Khan TM, Chan KG, Pusparajah P, Goh BH, Lee LH. Streptomyces as a Prominent Resource of Future Anti-MRSA Drugs. Front Microbiol 2018; 9:2221. [PMID: 30319563 PMCID: PMC6165876 DOI: 10.3389/fmicb.2018.02221] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 08/30/2018] [Indexed: 01/21/2023] Open
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) pose a significant health threat as they tend to cause severe infections in vulnerable populations and are difficult to treat due to a limited range of effective antibiotics and also their ability to form biofilm. These organisms were once limited to hospital acquired infections but are now widely present in the community and even in animals. Furthermore, these organisms are constantly evolving to develop resistance to more antibiotics. This results in a need for new clinically useful antibiotics and one potential source are the Streptomyces which have already been the source of several anti-MRSA drugs including vancomycin. There remain large numbers of Streptomyces potentially undiscovered in underexplored regions such as mangrove, deserts, marine, and freshwater environments as well as endophytes. Organisms from these regions also face significant challenges to survival which often result in the production of novel bioactive compounds, several of which have already shown promise in drug development. We review the various mechanisms of antibiotic resistance in MRSA and all the known compounds isolated from Streptomyces with anti-MRSA activity with a focus on those from underexplored regions. The isolation of the full array of compounds Streptomyces are potentially capable of producing in the laboratory has proven a challenge, we also review techniques that have been used to overcome this obstacle including genetic cluster analysis. Additionally, we review the in vivo work done thus far with promising compounds of Streptomyces origin as well as the animal models that could be used for this work.
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Affiliation(s)
- Hefa Mangzira Kemung
- Novel Bacteria and Drug Discovery Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,Biofunctional Molecule Exploratory Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
| | - Loh Teng-Hern Tan
- Novel Bacteria and Drug Discovery Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,Biofunctional Molecule Exploratory Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia
| | - Tahir Mehmood Khan
- Novel Bacteria and Drug Discovery Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,Biofunctional Molecule Exploratory Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,The Institute of Pharmaceutical Sciences (IPS), University of Veterinary and Animal Sciences (UVAS), Lahore, Pakistan
| | - Kok-Gan Chan
- Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.,International Genome Centre, Jiangsu University, Zhenjiang, China
| | - Priyia Pusparajah
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia
| | - Bey-Hing Goh
- Novel Bacteria and Drug Discovery Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,Biofunctional Molecule Exploratory Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Mueang Phayao, Thailand
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,Biofunctional Molecule Exploratory Research Group, Biomedicine Research Advancement Centre, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia.,Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia.,Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of Pharmaceutical Sciences, University of Phayao, Mueang Phayao, Thailand
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9
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Subscapular Abscess Caused by Panton-Valentine Leukocidin-Positive Staphylococcus aureus: An Atypical Presentation. Case Rep Orthop 2018; 2018:8256428. [PMID: 29984024 PMCID: PMC6015668 DOI: 10.1155/2018/8256428] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 04/29/2018] [Indexed: 11/17/2022] Open
Abstract
Subscapular abscess is an uncommon condition which requires early recognition followed by prompt surgical intervention. We present a case of spontaneous subscapular abscess following blunt trauma to the shoulder in a patient with a history of recurrent superficial soft tissue infections, in which Panton-Valentine leukocidin-producing S. aureus was identified as the infectious agent. This strain due to its virulence can lead to fatal infections in otherwise healthy individuals; therefore, a high index of suspicion is needed to investigate with an MRI to rule out abscess formation in a patient with acute shoulder girdle pain and negative joint aspirate. Urgent surgical intervention and targeted antimicrobial therapy against PVL-positive S. aureus in accordance with microbiologist yield good outcomes.
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10
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Irenji N, Pillai SKG, West-Jones JS. Serious life-threatening multifocal infection in a child, caused by Panton-Valentine leucocidin-producing Staphylococcus aureus (PVL-MSSA). BMJ Case Rep 2018; 2018:bcr-2017-222138. [PMID: 29871957 DOI: 10.1136/bcr-2017-222138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Groin pain is a frequently occurring complaint in presentations to the Emergency Department. Muscular sprain is often a differential diagnosis, however serious conditions such as pyomyositis should not be ignored. This case report presents a child with atraumatic right groin pain, which was initially diagnosed as a muscular sprain. The patient later re-presented out of hours to the Emergency Department with what was found to be extensive pelvic abscesses. He was subsequently found to have bilateral pneumonia and later developed a pericardial effusion and osteomyelitis of the right iliac bone, sacroiliac joint and sacrum. With multiple surgical interventions and appropriate antibiotics, he made a full recovery and was discharged home after a total admission time of 41 days. The causative organism was found to be Panton-Valentine leucocidin-positive methicillin-susceptible Staphylococcus aureus.
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Affiliation(s)
- Neda Irenji
- Department of Medicine, Abertawe Bro Morgannwg University Health Board, Swansea, UK
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Community-associated Staphylococcus aureus pneumonia among Greek children: epidemiology, molecular characteristics, treatment, and outcome. Eur J Clin Microbiol Infect Dis 2016; 35:1177-85. [PMID: 27140201 DOI: 10.1007/s10096-016-2651-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 04/15/2016] [Indexed: 10/21/2022]
Abstract
Staphylococcus aureus is an infrequent cause of community-associated (CA-SA) pneumonia in children. The aim of this study was to evaluate the clinical, epidemiological, microbiological, and molecular characteristics of CA-SA pneumonia among children hospitalized in two large tertiary care referral centers during an 8-year period. Cases of CA-SA pneumonia admitted between 2007 and 2014 were retrospectively examined through medical record review. Molecular investigation was performed for available strains; mecA, Panton-Valentine leukocidin (PVL) (lukS-lukF-PV), and fibronectin binding protein A (fnbA) genes were detected by polymerase chain reaction (PCR). Clones were assigned by agr groups, pulsed-field gel electrophoresis (PFGE), SCCmec, and multilocus sequencing typing (MLST). In total, 41 cases were recorded (boys, 61 %), with a median age of 4.3 months (range, 1-175). Methicillin-resistant S. aureus (MRSA) accounted for 31 cases (75.6 %). Complications included empyema (25/41, 61 %), pneumatoceles (7/41, 17 %), and lung abscess (1/41, 2.5 %). Intensive care unit (ICU) admission was required in 58.5 %. Two deaths occurred (4.9 %). Definitive therapy was based on vancomycin with or without other antibiotics (55.9 %), followed by clindamycin and linezolid (26.5 % each). All isolates were susceptible to vancomycin (MIC90 2 mg/L, range 1-2), teicoplanin, and linezolid, whereas 26.8 % were resistant to clindamycin. Among the 25 studied strains, 20 were mecA-positive (MRSA), carrying also the fnbA gene. Of these, 90 % belonged to the ST80-IV/agr3/PVL-positive clone. Methicillin-susceptible S. aureus (MSSA) strains showed polyclonality, 3/5 were PVL-positive, and 3/5 were fnbA-positive. MRSA and particularly the ST80-IV clone predominated among staphylococcal pneumonia cases in children. Treatment provided was effective in all but two patients, despite the relatively high minimum inhibitory concentration (MIC) of vancomycin and a high resistance to clindamycin.
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Özekinci T, Dal T, Yanık K, Özcan N, Can Ş, Tekin A, Yıldırım Hİ, Kandemir İ. Panton-Valentine leukocidin in community and hospital-acquired Staphylococcus aureus strains. BIOTECHNOL BIOTEC EQ 2014; 28:1089-1094. [PMID: 26019595 PMCID: PMC4433891 DOI: 10.1080/13102818.2014.976457] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Accepted: 07/28/2014] [Indexed: 11/11/2022] Open
Abstract
Staphylococcus aureus causes serious hospital-acquired (HA) and community-acquired (CA) infections. Skin and soft-tissue infections especially are sometimes caused by strains harbouring Panton-Valentine leukocidin (PVL). PVL belongs to a family of bi-component leukocidal toxins produced by staphylococci. It is a pore-forming toxin encoded by lukF-PV and lukS-PV. A total of 70 S. aureus strains: 38 (54%) methicillin-resistant (MRSA) and 32 (46%) methicillin-susceptible (MSSA), were isolated from patients admitted to Dicle University Hospital (Turkey). Identification of S. aureus and antibiotics-susceptibility testing were performed with PHOENIX 100. PVL genes and mecA genes were detected by polymerase chain reaction. Of the 70 studied strains, 36 ones (51%) were community acquired and 34 ones (49%) were hospital acquired . A total of 38 (54%) strains were positive for mecA (mecA+), of which 32 ones (84%) were HA. Of the mecA− strains, 30 (94%) were CA. Of the 70 studied strains, 12 (17%) strains were PVL+: 8 (22%) of the 36 CA strains and 4 (12%) of the 34 HA strains. Of the 12 PVL+ strains, 4 strains were mecA+. The PVL positivity rate was 25% in MSSA, whereas 10.5% in MRSA. Of the overall PVL+ strains, seven strains were obtained from wounds; four ones from skin abscess; and one from blood culture. Taken together, the obtained results showed a substantial level of PVL genes in the studied region. Although PVL is known as a common virulence factor of CA MRSA, HA MRSA isolates in our study showed a considerable rate of PVL positivity.
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Affiliation(s)
- Tuncer Özekinci
- Department of Medical Microbiology, Faculty of Medicine, Dicle University , Diyarbakır , Turkey
| | - Tuba Dal
- Department of Medical Microbiology, Faculty of Medicine, Yıldırım Beyazıt University , Ankara , Turkey
| | - Keramettin Yanık
- Department of Medical Microbiology, Faculty of Medicine, Ondokuz Mayıs University , Samsun , Turkey
| | - Nida Özcan
- Department of Medical Microbiology, Faculty of Medicine, Dicle University , Diyarbakır , Turkey
| | - Şükran Can
- Department of Medical Microbiology, Ergani State Hospital , Diyarbakır , Turkey
| | - Alicem Tekin
- Department of Medical Microbiology, Faculty of Medicine, Dicle University , Diyarbakır , Turkey
| | - Halil İbrahim Yıldırım
- Department of Genetics, Faculty of Veterinary Medicine, Dicle University , Diyarbakır , Turkey
| | - İdris Kandemir
- Department of Medical Microbiology, Faculty of Medicine, Dicle University , Diyarbakır , Turkey
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Riedweg-Moreno K, Wallet F, Blazejewski C, Goffard A. Successful management of Panton-Valentine leukocidine-positive necrotising pneumonia and A/H1N12009 influenzavirus coinfection in adult. BMJ Case Rep 2014; 2014:bcr-2013-201120. [PMID: 24436283 DOI: 10.1136/bcr-2013-201120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
This paper presents a case of community-acquired necrotising pneumonia due to Panton-Valentine leukocidine-positive methicillin-susceptible Staphylococcus aureus and A/H1N12009 influenzavirus co-infection in a 26-year-old woman. Despite the presence of pejorative prognostic factors, the clinical course of the patient was favourable.
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Affiliation(s)
- Karena Riedweg-Moreno
- Faculty of Medicine, Department of Microbiology, Lille University Hospital, Lille, France
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