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Host Gene Expression Profiling and In Vivo Cytokine Studies to Characterize the Role of Linezolid and Vancomycin in Methicillin-Resistant Staphylococcus aureus (MRSA) Murine Sepsis Model  [PDF]
Batu K. Sharma-Kuinkel, Yurong Zhang, Qin Yan, Sun Hee Ahn, Vance G. Fowler
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060463
Abstract: Linezolid (L), a potent antibiotic for Methicillin Resistant Staphylococcus aureus (MRSA), inhibits bacterial protein synthesis. By contrast, vancomycin (V) is a cell wall active agent. Here, we used a murine sepsis model to test the hypothesis that L treatment is associated with differences in bacterial and host characteristics as compared to V. Mice were injected with S. aureus USA300, and then intravenously treated with 25 mg/kg of either L or V at 2 hours post infection (hpi). In vivo alpha-hemolysin production was reduced in both L and V-treated mice compared to untreated mice but the reduction did not reach the statistical significance [P = 0.12 for L; P = 0.70 for V). PVL was significantly reduced in L-treated mice compared to untreated mice (P = 0.02). However the reduction of in vivo PVL did not reach the statistical significance in V- treated mice compared to untreated mice (P = 0.27). Both antibiotics significantly reduced IL-1β production [P = 0.001 for L; P = 0.006 for V]. IL-6 was significantly reduced with L but not V antibiotic treatment [P<0.001 for L; P = 0.11 for V]. Neither treatment significantly reduced production of TNF-α. Whole-blood gene expression profiling showed no significant effect of L and V on uninfected mice. In S. aureus-infected mice, L altered the expression of a greater number of genes than V (95 vs. 42; P = 0.001). Pathway analysis for the differentially expressed genes identified toll-like receptor signaling pathway to be common to each S. aureus-infected comparison. Expression of immunomodulatory genes like Cxcl9, Cxcl10, Il1r2, Cd14 and Nfkbia was different among the treatment groups. Glycerolipid metabolism pathway was uniquely associated with L treatment in S. aureus infection. This study demonstrates that, as compared to V, treatment with L is associated with reduced levels of toxin production, differences in host inflammatory response, and distinct host gene expression characteristics in MRSA sepsis.
Effect of granulocyte colony-stimulating factor in experimental methicillin resistant Staphylococcus aureus sepsis
Emine Alp, Suveyda Gozukucuk, Ozlem Canoz, Beyhan Kirmaci, Mehmet Doganay
BMC Infectious Diseases , 2004, DOI: 10.1186/1471-2334-4-43
Abstract: Experimental sepsis was performed in mice by intraperitoneal injection of MRSA isolate. Inoculum dose was estimated as 6 × 109/ml. Mice were randomised for the study into four group; control group (not receive any therapy), G-CSF group (1000 ng/daily, subcutaneously for 3 d), antibiotic group (vancomycin 25 or 50 mg/kg intraperitoneally every 12 hours for 7 d), and vancomycin+G-CSF group (at the same concentrations and duration). Autopsy was done within one hour after mice died. If mice was still alive at the end of seventh day, they were sacrificed, and autopsy was done. In all groups, the effect of G-CSF therapy on the survival, the number of the MRSA colonies in the lung, liver, heart, spleen, and peritoneal cultures, the histopathology of the lung, liver, heart and spleen was investigated.One hundred and six mice were used. There were no significant differences in survival rates and bacterial eradication in G-CSF group compared with control group, and also in antibiotic +G-CSF group compared with antibiotic alone group. These parameters were all significantly different in antibiotic alone group compared with control group. Histopathologically, inflammation of the lung and liver were significantly reduced in vancomycin (25 mg/kg)+G-CSF and vancomycin (50 mg/kg)+G-CSF subgroups, respectively (p < 0.01). The histopathological inflammation of the other organs was not significantly different in antibiotic+G-CSF group compared with antibiotic group and, also G-CSF group compared with control group.G-CSF treatment had no additional effect on survival and bacterial eradication in MRSA sepsis in nonneutropenic mice; and only a little effect on histopathology. G-CSF treatment is very expensive, likewise glycopeptides. The more interest in infection control measures, and prevent the spread of MRSA infections is more rational.Staphylococcus aureus is an extremely virulent pathogen, and causes serious and deep-seated infections (e.g. endocarditis, osteomyelitis) [1]. In rece
Therapy-refractory Panton Valentine Leukocidin-positive community-acquired methicillin-sensitive Staphylococcus aureus sepsis with progressive metastatic soft tissue infection: a case report
Joerg C Schefold, Fabrizio Esposito, Christian Storm, Dagmar Heuck, Anne Krüger, Achim J?rres, Wolfgang Witte, Dietrich Hasper
Journal of Medical Case Reports , 2007, DOI: 10.1186/1752-1947-1-165
Abstract: Panton Valentine Leukocidin (PVL) positive staphylococcal infection typically presents as life-threateninginfection of soft-tissues and bones [1,2]. PVL-positive staphylococcal infection may also lead to necrotizing pneumonia, a condition which can even be observed before the onset of soft-tissue or bone infection [3,4]. The underlying molecular mechanisms in regard to the progression of PVL-positive staphylococcal necrotizing pneumonia and respective methods of bacterial invasion have recently been elucidated [5,6]. The genes encoding the exotoxin PVL are typically present in community-acquired methicillin-sensitive S. aureus (CA-MSSA) [3], with about 2–5% of PVL-positive MSSA strains. Nevertheless, this varies markedly in different geographic locations. However, first cases of community-acquired methicillin-resistant S. aureus (CA-MRSA) have been reported. Clonal spread of PVL-positive strains and horizontal bacteriophage-dependent PVL-gene transfer thus contribute to an emerging health care problem [7,8]. Although the value of routine PVL testing in staphylococcal infection is currently unclear, both patient and household members should undergo PVL testing in severe or recurrent S. aureus infection in order to prevent the spreading of these strains. De-colonization of the patient and respective household members should then be achieved [9,10].We report the case of a 51-year old previously healthy immunocompetent Caucasian male who developed acute illness with fever, dyspnoea and expectoration of bloody sputum during a diving holiday in Croatia. The patient was admitted to a local hospital where empiric antibiotic therapy with azithromycin and ciprofloxacin for radiologically confirmed pneumonia was initiated. Before onset of the acute illness, symptoms suggesting previous (e.g. viral) respiratory tract infection were not observed. After 3 days, the patient was referred to our clinic via an ambulance air service.Upon initial examination, the patient presented with
Revisiting methicillin-resistant Staphylococcus aureus infections  [cached]
Waness Abdelkarim
Journal of Global Infectious Diseases , 2010,
Abstract: Within less than 50 years, methicillin-resistant Staphylococcus aureus (MRSA) made a tremendous impact worldwide. It is not limited to medical facilities and healthcare institutions anymore. Indeed since two decades, cases of MRSA infections arising from the community among apparently healthy individuals are increasing. In this paper, I will present a case of community-associated MRSA sepsis followed by a comprehensive review about the history, pathogenesis, epidemiology, clinical presentations, diagnostic modalities, therapeutic options, contributing factors, growing cost and other pertinent elements of this newly evolving epidemic of MRSA infections.
Staphylococcus aureus methicillin-resistance mechanisms  [PDF]
Petrovi?-Jeremi? Ljiljana,Kulji?-Kapulica Nada,Mirovi? Veljko,Koci? Branislava
Vojnosanitetski Pregled , 2008, DOI: 10.2298/vsp0805377p
Abstract: Background/Aim. In many hospitals in the world and in our country, the spread of methicillin-resistant Staphylococcus aureus (MRSA) is so wide that nowdays vancomycin is recommended for empiric treatment of staphylococcal life threatening infections (sepsis, pneumonia) instead of beta-lactam antibiotics. The aim of this study was to determine the production of beta-lactamases in hospital and community isolates of staphyloococus aureus, i. e. hospital associated MRSA (HA-MRSA) and community associated MRSA (CA-MRSA), the presence of homogeneous and heterogeneous type of methicillin resistance, and border-line resistance in Staphylococcus aureus (BORSA). The aim of this study was also to determine if there was a statistically significant difference between mechanisms of resistance in HA-MRSA and CA-MRSA. Methods. A total 216 clinical Staphylococcus aureus isolates from the General Hospital in the town of Cuprija and 186 ambulance Staphylococcus aureus isolates from the community were examined for the presence of methicillin-resistance using disk-diffusion test with penicillin disk (10 ij), oxacillin disk (1 μg) and cefoxitin disk (30 μg). Betalactamases production was detected by nitrocefin disk and betalactamase tablets. Determination of oxacillin minimum inhibitory concentracion (MIC) was done by agar-dilution method. Results. The prevalence of HA-MRSA was 57.4%, and CA-MRSA was 17.7% (p < 0.05). There was a higher rate of heterogeneous type of resistance among clinical MRSA isolates (11.1%) compared with ambulance ones (3.8%) (p < 0.05). The rates of beta-lactamases production were similar among hospital associated isolates (97.5%), as well as in the community associated isolates (95.5%) (p > 0.05). There were 4.6 % of BORSA hospital isolates and 3.3 % of BORSA ambulance isolates (p > 0.05). Conclusion. The frequency of MRSA isolates in hospital was significantly higher than in community, as well as the heterogeneous type of resistance. The frequency of BORSA isolates and production of betalactamases were higher among hospital Staphylococcus aureus isolates, but the difference is not significant.
Whole Genome Analysis of a Community-Associated Methicillin-Resistant Staphylococcus aureus ST59 Isolate from a Case of Human Sepsis and Severe Pneumonia in China  [PDF]
Tingting Qu, Ye Feng, Yan Jiang, Peiqiong Zhu, Zeqing Wei, Yan Chen, Michael Otto, Yunsong Yu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089235
Abstract: We report a case of necrotizing pneumonia in a young patient caused by community acquired-methicillin resistant Staphylococcus aureus (CA-MRSA) in a teaching hospital in the People’s Republic of China. The patient had a typical clinical presentation and was successfully treated with antibiotics and intravenous immunoglobulin. A CA-MRSA strain, named SA268, was isolated from the blood of the patient. The isolate was susceptible to most antimicrobial agents, except cephalosporins, penicillins, and β-lactamase inhibitor combinations. Multi-locus sequence typing (MLST) assigned SA268 to ST59, a clone widely spread in eastern Asia. The strain was positive for Panton Valentine Leukocidin (PVL)-encoding genes and SCCmec type V. We sequenced the complete genome of the SA268 isolate. The genome of SA268 was almost identical to that of the Taiwanese ST59 CA-MRSA strains M013 and SA957. However, we observed several differences in gene composition, which included differences in the SCCmec element and several lipoprotein genes that were present in the Taiwanese strains but absent from SA268.
Catalase-negative, methicillin-resistant Staphylococcus aureus as a cause of septicemia
Carvalho, Ana Lúcia Innaco de;Zanella, Rosemeire Cobo;Yoshikawa, Luciane Parra;Bokermann, Sérgio;Guerra, Maria Luiza L.S.;Atobe, Jane Harumi;Lovgren, Marguerite;
Jornal Brasileiro de Patologia e Medicina Laboratorial , 2003, DOI: 10.1590/S1676-24442003000100009
Abstract: a catalase-negative methicillin-resistant staphylococcus aureus (mrsa) was isolated from blood, venous catheter spike and bone marrow collected from an hiv-positive man with lobar pneumonia and sepsis after ten days of hospitalization. the isolate was resistant to oxacillin (positive for penicillin-binding protein 2'), ceftriaxone, clindamycin and clarithromycin, and susceptible to vancomycin. this is the first case of septicemia due to a catalase-negative s. aureus reported in brazil, and, to our knowledge, it is the first case of catalase-negative mrsa reported in the literature. we believe that the patient acquired the s. aureus infection within the hospital environment since it was isolated ten days after hospitalization, it was isolated in a venous catheter spike, and the antibiotic resistance profile is similar to other s. aureus isolates recovered from infections in our hospital.
Catalase-negative, methicillin-resistant Staphylococcus aureus as a cause of septicemia  [cached]
Carvalho Ana Lúcia Innaco de,Zanella Rosemeire Cobo,Yoshikawa Luciane Parra,Bokermann Sérgio
Jornal Brasileiro de Patologia e Medicina Laboratorial , 2003,
Abstract: A catalase-negative methicillin-resistant Staphylococcus aureus (MRSA) was isolated from blood, venous catheter spike and bone marrow collected from an HIV-positive man with lobar pneumonia and sepsis after ten days of hospitalization. The isolate was resistant to oxacillin (positive for penicillin-binding protein 2'), ceftriaxone, clindamycin and clarithromycin, and susceptible to vancomycin. This is the first case of septicemia due to a catalase-negative S. aureus reported in Brazil, and, to our knowledge, it is the first case of catalase-negative MRSA reported in the literature. We believe that the patient acquired the S. aureus infection within the hospital environment since it was isolated ten days after hospitalization, it was isolated in a venous catheter spike, and the antibiotic resistance profile is similar to other S. aureus isolates recovered from infections in our hospital.
Frequency of methicillin resistant Staphylococcus aureus in health care  [cached]
Somayeh Rahimi-Alang,Mehdi Asmar,Fatemeh Cheraghali,Sarah Yazarlou
Zahedan Journal of Research in Medical Sciences , 2011,
Abstract: Background: Methicillin resistant Staphylococcus aureus (MRSA) is one of the most important pathogen in hospitals. Healthcare personnel are the main source of nosocomial infections and identification and control of MRSA carriers can reduce incidence of infections. The aim of this study was to determine the prevalence of MRSA and their antibiotic susceptibility profile among healthcare workers in Gorgan.Materials and Method: 333 healthcare workers were participated in this cross-sectional study in 2009. Samples were taken with sterile cotton swabs from both anterior nares and hands. Swabs were plated immediately on to the mannitol salt agar. Suspected colonies were confirmed as S. aureus by Gram staining, catalase, coagulase and DNase tests. Minimum inhibition concentration by micro dilution broth method was used to determine methicillin resistant strains. Antimicrobial susceptibility to other antibiotics was performed according to NCCLS guidelines by disc diffusion method.Result: Frequency of S.aureus and MRSA carriers among healthcare workers was 24% and 3% respectively. The highest rate of S. aureus and MRSA carriers were observed in operating room staff. Resistance to penicillin was seen in 97.5% of isolates and all strains were sensitive to vancomycin.Conclusions: Frequency of S. aureus and MRSA in healthcare workers was median and rather low respectively. Continual monitoring and control of carriers can reduce distribution of this organism and their infections
Sepse por Staphylococus aureus resistente à meticilina adquirida na comunidade no sul do Brasil
Gelatti, Luciane Cristina;Sukiennik, Tereza;Becker, Ana Paula;Inoue, Fernanda Matsiko;Carmo, Mirian Silva do;Castrucci, Fernanda Marques da Silva;Pignatari, Ant?nio Carlos Campos;Ribeiro, Luis Carlos;Bonamigo, Renan Rangel;Azevedo, Pedro Alves d';
Revista da Sociedade Brasileira de Medicina Tropical , 2009, DOI: 10.1590/S0037-86822009000400019
Abstract: methicillin-resistant staphylococcus aureus was initially described as a typical microorganism acquired in nosocomial infections. however, over recent years, community-acquired methicillin-resistant staphylococcus aureus has been a cause of skin and soft-tissue infections. serious infections such as pneumonia and sepsis can also occur. this report describes a case of sepsis in a child that was complicated by pneumonia secondary to soft tissue lesions that were due to community-acquired methicillin-resistant staphylococcus aureus in southern brazil. the patient was attended at the emergency unit with a history of injury caused by lower-limb trauma that evolved to cellulitis, pneumonia and sepsis.
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