Hospital-acquired MRSA Strains Research Articles

Detection of mecA Genes in Hospital-Acquired MRSA and SOSA Strains Associated with Biofilm Formation.

Methicillin-resistant (MR) Staphylococcus aureus (SA) and others, except for Staphylococcus aureus (SOSA), are common in healthcare-associated infections. SOSA encompass largely coagulase-negative staphylococci, including coagulase-positive staphylococcal species. Biofilm formation is encoded by the icaADBC operon and is involved in virulence. mecA encodes an additional penicillin-binding protein (PBP), PBP2a, that avoids the arrival of β-lactams at the target, found in the staphylococcal cassette chromosome mec (SCCmec). This work aims to detect mecA, the bap gene, the icaADBC operon, and types of SCCmec associated to biofilm in MRSA and SOSA strains. A total of 46% (37/80) of the strains were S. aureus, 44% (35/80) S. epidermidis, 5% (4/80) S. haemolyticus, 2.5% (2/80) S. hominis, 1.25% (1/80) S. intermedius, and 1.25% (1/80) S. saprophyticus. A total of 85% were MR, of which 95.5% showed mecA and 86.7% β-lactamase producers; thus, Staphylococcus may have more than one resistance mechanism. Healthcare-associated infection strains codified type I-III genes of SCCmec; types IV and V were associated to community-acquired strains (CA). Type II prevailed in MRSA mecA strains and type II and III in MRSOSA (methicillin-resistant staphylococci other than Staphylococcus aureus). The operon icaADBC was found in 24% of SA and 14% of SOSA; probably the arrangement of the operon, fork formation, and mutations influenced the variation. Methicillin resistance was mainly mediated by the mecA gene; however, there may be other mechanisms that also participate, since biofilm production is related to genes of the icaADBC operon and methicillin resistance was not associated with biofilm production. Therefore, it is necessary to strengthen surveillance to prevent the spread of these outbreaks both in the nosocomial environment and in the community.

Community-acquired Methicillin-resistant Staphylococcus Aureus Pneumonia: A Diagnostic Challenge

Even though methicillin-resistant Staphylococcus aureus (MRSA) is considered a source of nosocomial pneumonia, a few cases have likewise depicted instances of community-acquired pneumonia (CAP) among healthy individuals that were caused by MRSA. Mostly CA-MRSA causes skin and soft tissue infection but can be responsible for severe invasive infection with higher morbidity. Invasive CA-MRSA requires aggressive management to prevent complications. CA-MRSA strains are now recognized as distinct clonal entities that differ from traditional hospital-acquired MRSA (HA-MRSA) strains. The increasing prevalence of MRSA in the community is an important public health problem, which needs increased vigilance in the diagnosis and management of suspected and confirmed staphylococcal infections. We present an intense case of CAP brought about by MRSA with impending respiratory failure in a 19-year-old male, who presented with acute febrile illness with swelling over lips with no co-morbid and insignificant past medical history. Through this case, we intend to increase awareness among physicians about the growing role of CA-MRSA in the population; they should be meticulous in treating patients with CA-MRSA, and be aware of the complications of this disease and the appropriate empiric and target antibiotics regimen for such infections, whenever it is suspected, to enhance better clinical outcomes.

Occurrence of Staphylococcus aureus in milk and antibacterial properties of some herbal extracts on milk and hospital-acquired strains

Staphylococcus aureus is a remarkable infectious agent, and with the development of antibiotic resistance by S. aureus, finding new, effective, and safe alternative therapeutic options in animals and humans is crucially demanded. In this study, the occurrence of S. aureus was explored by collecting nonmastitis bovine milk samples first, and then the effects of herbal extracts on methicillinresistant S. aureus (MRSA) strains isolated from cow's milk and humans in the hospitals were investigated. The occurrences of S. aureus in bovine raw milk samples were 13.4%. All raw milk S. aureus isolates were fully susceptible to cefoxitin, ceftiofur, penicillin G, and enrofloxacin. However, resistance was recorded for methicillin, streptomycin, tylosin, and sulfamethoxazole-trimethoprim. The most antibacterial resistance was recorded for oxytetracycline with 40% (intermediate resistance) and 15% (full resistance) respectively. The hospital-acquired S. aureus isolates were entirely resistant to methicillin and penicillin and were susceptible to some antibiotics. Sulfamethoxazole-trimethoprim was the most effective antibiotic with 83.4%. The antimicrobial activities of five medicinal herbs against raw milk S. aureus and hospital-acquired S. aureus isolates were assessed with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The findings affirmed that Rosmarinus officinalis and Nigella sativa acted as potent antibacterial agents on S. aureus strain obtained for nonmastitis bovine raw milk and hospital-acquired MRSA strains. The efficiency of these herbs against S. aureus isolates indicates their applicability as an antibacterial agent for alternative therapy in dairy products and human health and provokes further investigations in this area.

Molecular Evaluation of Traditional Chicken Farm-Associated Bioaerosols for Methicillin-Resistant Staphylococcus aureus Shedding.

The outbreak of airborne pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) through bioaerosol, and their molecular characterization around domestic poultry farming areas, was not completely understood. This imposes risk of a MRSA-associated health threat for the relevant livestock food production units. To address this issue, the present study investigated the role of bioaerosol in transmitting MRSA strains in poultry house settings by combining molecular typing, phylogenetic classification, antibiotic susceptibility, and virulence gene distribution patterns. The present study highlights that all 18 bioaerosol and stool samples collected were MRSA positive, with a unique set of virulence factors. Out of 57 isolated MRSA isolates, 68.4% and 19.3% consisted of SCCmec I and IV elements, respectively, which are commonly linked with hospital-acquired and livestock-associated MRSA strains. It is worth noting that the exfoliative toxin eta and etb genes were carried by 100% and 70.2% of all isolates, respectively. Only 17.5% of strains showed the presence of enterotoxin entC. These MRSA isolates were resistant to chloramphenicol (C), ciprofloxacin (CIP), clindamycin (DA), erythromycin (E), and tetracycline (T), signifying their multi-drug resistance traits. A cluster of phylogenetic analysis described that 80.7% and 15.8% of total isolates belonged to Staphylococcus aureus protein A (spa) type t002 and t548. Whereas 3.5% were reflected as a new spa type. Additionally, as per the chi-squared test score value, these two spa types (t002 and t548) have a distribution correlation with HA-MRSA and LA-MRSA in all the samples (p < 0.005, chi-squared test; degree of freedom = 1). Ultimately, this study highlights the prevalence of MRSA colonization in the conventional poultry farm environment, showing the risk of bioaerosol transmission, which needs epidemiological attention and prevention strategies.

Antagonistic Effect of Colistin on Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus in In Vitro and In Vivo Studies.

As concerns arise that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concurrent colistin administration, we evaluated the effect of colistin on vancomycin efficacy against MRSA via in vitro and in vivo studies. Among MRSA blood isolates collected in a tertiary-care hospital, we selected representative strains from community-associated MRSA strains (CA-MRSA; ST72-MRSA-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA; ST5-MRSA-SCCmec II). USA CA-MRSA (USA300), HA-MRSA (USA100), N315 (New York/Japan clone), and a MRSA standard strain (ATCC 43300) were used for comparison. We performed checkerboard assays to identify changes in the vancomycin MIC of MRSA following colistin exposure and evaluated the effect of a vancomycin-colistin combination using time-kill assays. We also assessed the in vivo antagonistic effect by administering vancomycin, colistin, and a combination of these two in a neutropenic murine thigh infection model. In the checkerboard assays, vancomycin MICs of all MRSA strains except N315 were increased by from 0.25 to 0.75 μg/ml following colistin exposure. However, the time-kill assays indicated antagonism only against ST5-MRSA and USA100, when the vancomycin concentration was twice the MIC. In the murine thigh infection model with ST5-MRSA and USA100, vancomycin monotherapy reduced the number of CFU/muscle >1 log10 compared to a combination treatment after 24 h in ST5-MRSA, indicating an antagonistic effect of colistin on vancomycin treatment. This study suggests that exposure to colistin may reduce the susceptibility to vancomycin of certain MRSA strains. Combination therapy with vancomycin and colistin for multidrug-resistant pathogens might result in treatment failure for concurrent MRSA infection.

204. Antagonistic Effect of Colistin on Vancomycin Activity Against Methicillin-Resistant Staphylococcus aureus in in vitro and in vivo Studies

BackgroundThere is a concern that the vancomycin MIC of methicillin-resistant Staphylococcus aureus (MRSA) could be increased by concomitant colistin administered against multidrug-resistant gram-negative pathogen.MethodsWe confirmed the molecular genotypes of MRSA blood isolates collected in a tertiary hospital in Seoul, South Korea, and selected representative strains from the community-associated MRSA strains (CA-MRSA, ST72-SCCmec IV) and hospital-acquired MRSA strains (HA-MRSA, ST5-SCCmec II). USA CA-MRSA (USA300, ST8-SCCmec IV) and MRSA standard strain (ATCC 43300, ST39-SCCmec II) were also used for comparison with representative. We identified changes of the vancomycin MIC in MRSA by colistin exposure in a checkerboard assay and performed a time-kill assay to evaluate the combined effect of vancomycin and colistin on MRSA. In addition, we administered vancomycin, colistin, and combination of two antibiotics, respectively, to a neutropenic murine thigh infection model to evaluate the in vivo antagonistic effect of colistin on vancomycin treatment.ResultsIn the checkerboard assay, all 4 MRSA strains showed a tendency for the vancomycin MIC to increase along with increasing concentrations of colistin. However, the time-kill assay showed the antagonism of vancomycin and colistin only against ST5-MRSA, when vancomycin concentration was 2 times the vancomycin MIC (Figure 1). No antagonism was observed in other strains. In the murine thigh infection model of ST5-MRSA, vancomycin monotherapy showed a significant log CFU reduction compared with a combination of vancomycin and colistin at 24 hours, demonstrating the antagonistic effect of vancomycin and colistin combination (Figure 2).ConclusionThis study showed that exposure of colistin to certain MRSA strains may reduce the susceptibility to vancomycin. Combination therapy with vancomycin and colistin for MDR pathogens infections might result in treatment failure for concurrent MRSA infection. Disclosures All authors: No reported disclosures.

Multilocus sequence typing and antibiotic resistant patterns of the meticillin-resistant Staphylococcus aureus isolates from different clinical specimens

Backgrounds: Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging threat worldwide. Community-associated-MRSA strains differ from hospital-acquired MRSA strains in their genetic backgrounds, pathogenicity, and antibiotic susceptibilities. Although few studies have reported the epidemiology of the different community-associated-MRSA and hospital-acquired-MRSA clones present, there are insufficient data available on MRSA characteristics in Iran. The present cross-sectional study was conducted to explore the prevalence of MRSA, the antimicrobial susceptibility of the strains, and the molecular epidemiology of such MRSA isolates from a hospital in Tabriz, Iran. Methods: S. aureus isolates were collected from patients with clinical signs and symptoms of infection admitted to Imam Reza Hospital, from September 2016 to March 2017 in Tabriz, Iran. Standard conventional biochemical tests for identification of the isolates were performed on colonies from primary cultures. The antibiotic susceptibility testing was performed using the standardized Kirby–Bauer disc-diffusion method on Mueller–Hinton agar. All methicillin-resistant isolates were archived for subsequent molecular tests, including PCR for mecA gene and multilocus sequence typing. Results: Among 39 S. aureus isolates enrolled, 33.3% (13/39) were identified as MRSA strains. Antibiotic susceptibilities to erythromycin, ciprofloxacin, and clindamycin, were measured as, 48.7, 46.2, and 35.9%, respectively. All of the 39 isolates were susceptible to vancomycin and linezolid. Sequence type (ST)-238 was the predominant clone (15.3%), and ST585, ST1, ST88, ST45, ST158, ST1097, ST2373, and ST2873 were other detected sequence type. In addition, two undetermined sequence type (a sequence type was not matched to any sequence type identified) were detected in this study. Conclusion: ST238 strains, which were previously not found as MRSA, could now widely distribute in Iranian population. In addition, the resistance rate of MRSA strains against multiple classes of antibiotics should be considered when selecting empirical antibiotics for MRSA infections in Iran.

Change in genotype of methicillin-resistant Staphylococcus aureus (MRSA) affects the antibiogram of hospital-acquired MRSA.

Recently, the dissemination of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) into hospitals has frequently been reported worldwide. Hospital-acquired MRSA (HA-MRSA) strains exhibit high-level resistance to multiple antimicrobial agents, whereas CA-MRSA strains are usually susceptible to non-β-lactams. Thus, it is predicted that the antibiogram of the HA-MRSA population would change along with the change in genotype of MRSA. Here, we investigated the changes in the MRSA population along with the MRSA antibiogram in a hospital between 2010 and 2016. Staphylococcal cassette chromosome (SCC) mec typing showed that the predominant HA-MRSA strains in the hospital dramatically changed from SCCmec type II, which is the major type of HA-MRSA, to SCCmec type IV, which is the major type of CA-MRSA. Multilocus sequence typing revealed that the predominant SCCmec type IV strain was a clonal complex (CC) 8 clone, which is mainly found among CA-MRSA. Furthermore, the CC1-SCCmec type IV (CC1-IV) clone significantly increased. Both the CC8-IV and CC1-IV clones exhibited high antimicrobial susceptibility. The antibiogram change of the HA-MRSA population was consistent with the antimicrobial susceptibilities and increased prevalence of the CC8-IV and CC1-IV clones. Our data reveal that the change in the genotypes of MRSA strains could impact the antibiogram of HA-MRSA population.

Role of SCCmec type in resistance to the synergistic activity of oxacillin and cefoxitin in MRSA

β-lactam antibiotics target penicillin-binding proteins (PBPs) preventing peptidoglycan synthesis and this inhibition is circumvented in methicillin resistant Staphylococcus aureus (MRSA) strains through the expression of an additional PBP, named PBP2A. This enzyme is encoded by the mecA gene located within the Staphylococcal Chromosome Cassette mec (SCCmec) mobile genetic element, of which there are 12 types described to date. Previous investigations aimed at analysing the synergistic activity of two β-lactams, oxacillin and cefoxitin, found that SCCmec type IV community-acquired MRSA strains exhibited increased susceptibility to oxacillin in the presence of cefoxitin, while hospital-acquired MRSA strains were unaffected. However, it is not clear if these differences in β-lactam resistance are indeed a consequence of the presence of the different SCCmec types. To address this question, we have exchanged the SCCmec type I in COL (HA-MRSA) for the SCCmec type IV from MW2 (CA-MRSA). This exchange did not decrease the resistance of COL against oxacillin and cefoxitin, as observed in MW2, indicating that genetic features residing outside of the SCCmec element are likely to be responsible for the discrepancy in oxacillin and cefoxitin synergy against these MRSA strains.

Molecular characterisation of Panton–Valentine leucocidin-producing methicillin-resistant Staphylococcus aureus clones isolated from the main hospitals in Taif, KSA

Introduction: Panton–Valentine leucocidin (PVL) is a bicomponent pore-forming cytolytic toxin encoded by the lukF-PV and lukS-PV genes. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) may carry the pvl genes which may be related to increased disease severity. This study aimed to characterise the PVL-producing MRSA recovered from different Taif Hospitals, Saudi Arabia. Methods: The study included 45 hospital-acquired-MRSA (HA-MRSA) and 26 CA-MRSA strains which were identified from 445 S. aureus strains isolated from different clinical samples. MRSA strains were identified by standard oxacillin salt agar screening procedure and by the detection of the mecA gene by the polymerase chain reaction (PCR). Detection of the S. aureus-specific femA, mecA and pvl genes was performed by multiplex PCR. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis was done for coagulase (coa) gene. Results: The staphylococcal cassette chromosome mec types of the 45 HA-MRSA strains were Type I (n = 24), Type II (n = 7) and Type III (n = 14) whereas the 26 CA-MRSA strains were Type IV (n = 14), Type V (n = 11) and one isolate was non-typeable. All the HA-MRSA and six CA-MRSA strains were PVL-negative PCR-RFLP analysis of coa gene showed that PVL-positive MRSA (n = 20) isolates showed six different patterns, and five patterns were shared by PVL-positive methicillin-susceptible S. aureus (MSSA). The eighth pattern was the most frequent in both MRSA and MSSA. Conclusion: PVL is more frequent among CA-MRSA than MSSA. All the HA-MRSA and 25% of CA-MRSA strains were negative for PVL. The pvl gene was related to the severity of infection but not related to coa gene RFLP pattern.

Tetracyclic indolines as a novel class of β-lactam-selective resistance-modifying agent for MRSA

Antibiotic-resistant bacterial infections have seen a marked increase in recent years, while antibiotic discovery has waned. Resistance-modifying agents (RMA) offer an intriguing alternative strategy to fight against resistant bacteria. Here we report the discovery, antibiotic profiling, and structure-activity relationships of a novel class of RMAs, tetracyclic indolines. These selectively potentiate β-lactam antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) without antibacterial or β-lactamase inhibitory activity on their own. The most potent analogue, 6a, showed strong potentiation of amoxicillin/clavulanic acid in a variety of hospital-acquired and community-acquired MRSA strains with low mammalian toxicity. These compounds may be further developed to extend the clinic life span of β-lactam antibiotics.

Epidemiological and Drug-Resistance Types of Methicillin-Resistant Staphylococcus Aureus Strains Isolated From Surgical and Transplantation Ward Patients During 2010 to 2011

BackgroundThe increasing prevalence of multi-drug–resistant methicillin-resistant Staphylococcus aureus (MRSA) is a substantial problem in hospitals worldwide, especially in wards with immunocompromised patients undergoing organ transplant. Epidemiological characteristics and antibiotic susceptibility profiles of hospital-acquired (HA) MRSA strains isolated from surgical/transplantation ward patients were studied. MethodsWe analyzed 26 HA-MRSA strains isolated from 22 patients hospitalized at 3 different surgical and transplantation wards at a Warsaw clinical hospital during 2010 to 2011. Eleven patients were MRSA-asymptomatic carriers. Strain relatedness was evaluated through the use of multi-locus sequence typing (MLST), multi-locus variable-number tandem repeat analysis (MLVA), and random amplified polymorphic DNA/arbitrarily primed PCR (RAPD) methods. Antibiotic susceptibility was assessed the use of routine diagnostic methods. ResultsThe evaluated strains belonged to 4 clonal complexes (CCs) and 4 sequence types (STs): CC30/ST36 (65.4%), CC8/ST8 (15.4%), CC5/ST1827 (11.5%), and CC1/ST1 (7.7%). Six MLVA types and 6 RAPD types were isolated. A ciprofloxacin-, erythromycin-, and clindamycin-resistant CC30/ST36 clone (MLVA type 1, RAPD type 1A) was isolated in all wards. The isolated HA-MRSA strains were most often resistant to ciprofloxacin (100%), erythromycin (96.2%), clindamycin (84.6%), and gentamycin (30.8%). ConclusionsA ciprofloxacin-, erythromycin-, and clindamycin-resistant HA-MRSA ST36 CC30 clone, which prevailed on transplantation wards in the years 2010 to 2011, is probably one of the international epidemic clones named UK EMRSA-16 or USA200.

73 Impact of community-acquired MRSA and hospital-acquired MRSA on pulmonary function of CF patients

Objective Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection affects both pulmonary function and survival of CF patients. Few reports have investigated the genetic background of MRSA strains involved in persistent lung infection. This study compares lung function decline in CF patients persistently infected by community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA). Methods Seventy-five patients attending five Italian CF centers and persistently infected by MRSA were studied. One strain/year/patient was analyzed. SCCmec analysis was performed as previously described in order to characterize CA- and HA-MRSA strains. The mean annual FEV 1 decline was evaluated for each patient. Results Forty-nine out of 75 (65%) patients maintained the same SCCmec type over time and the mean duration of infection was 3.1 years. Twenty-five patients (mean age 20.6 years) were persistently infected by HA-MRSA and 24 (mean age 18.4 years) by CA-MRSA. The prevalence of chronic P. aeruginosa infection was 52% and 29% in the HA- and CA-MRSA group respectively. The yearly mean FEV 1 decline for patients harboring HA-MRSA and CA-MRSA was –1.12±4.7 and –2.2±4 respectively. Conclusion Most of the studied patients maintained the same SCCmec type for several years. Patients infected by CA-MRSA showed more FEV1 decline in comparison with HA-MRSA infected patients. However this difference is not statistically significant. The knowledge of genetic background of MRSA strains should be improved in order to understand the clinical impact of persistent MRSA infection and optimize prevention and treatment strategies. Grant RF-2010-2316176 Bando Ricerca Finalizzata

Reduction of the Peptidoglycan Crosslinking Causes a Decrease in Stiffness of the Staphylococcus aureus Cell Envelope

We have used atomic-force microscopy (AFM) to probe the effect of peptidoglycan crosslinking reduction on the elasticity of the Staphylococcus aureus cell wall, which is of particular interest as a target for antimicrobial chemotherapy. Penicillin-binding protein 4 (PBP4) is a nonessential transpeptidase, required for the high levels of peptidoglycan crosslinking characteristic of S. aureus. Importantly, this protein is essential for β-lactam resistance in community-acquired, methicillin-resistant S. aureus (MRSA) strains but not in hospital-acquired MRSA strains. Using AFM in a new mode for recording force/distance curves, we observed that the absence of PBP4, and the concomitant reduction of the peptidoglycan crosslinking, resulted in a reduction in stiffness of the S. aureus cell wall. Importantly, the reduction in cell wall stiffness in the absence of PBP4 was observed both in community-acquired and hospital-acquired MRSA strains, indicating that high levels of peptidoglycan crosslinking modulate the overall structure and mechanical properties of the S. aureus cell envelope in both types of clinically relevant strains. Additionally, we were able to show that the applied method enables the separation of cell wall properties and turgor pressure.

Molecular characterization of methicillin-resistant Staphylococcus aureus isolated from tertiary care hospitals.

Methicillin-resistant S. aureus (MRSA) tends to be resistant to multiple antibiotics. Methicillin resistance is conferred by the acquisition of the mecA gene, which is carried by a mobile genetic element called the staphylococcal cassette chromosome mec (SCCmec). There are five major types of SCCmec elements (I-V). The majority of hospital-acquired MRSA (HA-MRSA) strains carry SCCmec types I, II, or III, whereas community-acquired MRSA (CA-MRSA) strains carry SCCmec types IV or V. In addition, Panton-Valentine Leucocidin (PVL) is a gene encoding a powerful cytotoxin that is strongly associated with CA-MRSA strains. The present study was aimed to identify the types of SCCmec and PVL genes among clinical MRSA isolates. This study was conducted in 5 tertiary care hospitals in Makkah city from March to September of 2012. A total of 206 S. aureus clinical isolates were analysed using standard microbiological methods. Multiplex PCR was performed on genomic DNA from MRSA isolates in order to identify the types of SCCmec. In addition, PCR was performed to detect the PVL gene among the isolates. Of the 206 S. aureus isolates, 114 (55.3%) were MRSA, and 100 of the MRSA isolates carried the mecA gene. RESULTS from SCCmec typing revealed that 3% were type I; 9% were type II; 47% were type III, and 29% were type IV. Nineteen per cent of the isolates harboured the PVL gene. Furthermore, there was a statistically significant correlation between the presence of the PVL gene and SCCmec type IV. The virulence of MRSA strains is increasing in both hospital and community settings in Makkah, highlighting the importance of their rapid identification in order to appropriately control infection.

Experimental phage therapy against lethal lung-derived septicemia caused by Staphylococcus aureus in mice

Nosocomial respiratory infections caused by methicillin-resistant Staphylococcus aureus (MRSA) can progress to lethal systemic infections. Bacteriophage (phage) therapy is expected to be effective against these critical infections. Previously, phage S13′ was proposed as a potential therapeutic phage. We here examined phage treatment in a mouse model of lung-derived septicemia using phage S13′. Intraperitoneal phage administration at 6 h postinfection reduced the severity of infection and rescued the infected mice. Phage S13′ can efficiently lyse hospital-acquired MRSA strains causing pneumonia-associated bacteremia in vitro. Thus, phage therapy may be a possible therapeutic intervention in staphylococcal lung-derived septicemia.

Phenotypic and Genotypic Characterization of Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA) from Different Sources in China

A diverse collection of 261 Staphylococcus aureus strains from human, animal, food, and environmental sources were tested for the presence and type of SCCmec elements, antibiotic susceptibility to various antibiotics, and non-ß-lactam antibiotic resistance genes. About 18.39% (48/261) of strains were methicillin-resistant S. aureus (MRSA) including 29.75% (36/121) human strains of which 29 strains were hospital-acquired MRSA (HA-MRSA) and 7 strains were community-associated MRSA (CA-MRSA) and 19.67% (12/61) animal strains that all were CA-MRSA strains. The percentage of CA-MRSA strains from animals was significantly higher than that from human (p<0.01). Most of MRSA strains and a part of methicillin-susceptible S. aureus (MSSA) strains harbored unique combinations of non-ß-lactamase genes aac(6')/aph(2″), aph(3')-III, ant (4',4″), ermA, ermC, mrsA, tetM, and tetK. Antibiotic resistance genes were detected more frequently in HA-MRSA strains than in CA-MRSA strains (p<0.01). MRSA strains and MSSA strains had 22 and 39 antibiotic profiles to 15 tested antibiotics, respectively. The resistant proportion was higher in HA-MRSA strains than in CA-MSSA strains for various antibiotics, as well as higher in MRSA strains than in MSSA strains. Animal MRSA reservoirs (particularly pigs and cows) might represent an important source of human CA-MRSA. CA-MRSA strains might acquire more different resistance genes gradually, depending on the selective pressure of antibiotics in different regions or environments. CA-MRSA is not yet endemic in China, but could be prevalent in future, contributing to its acquiring more resistance genes and huge animal sources. Infection with multidrug-resistant MSSA strains acquired from food, animal, and human sources might also become a significant problem for human medicine, which warrants further study.

Comparative Pharmacodynamics of the New Oxazolidinone Tedizolid Phosphate and Linezolid in a Neutropenic Murine Staphylococcus aureus Pneumonia Model

Tedizolid phosphate (TR-701) is a novel oxazolidinone prodrug (converted to the active form tedizolid [TR-700]) with potent Staphylococcus aureus activity. The current studies characterized and compared the in vivo pharmacokinetic/pharmacodynamic (PD) characteristics of TR-701/TR-700 and linezolid against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in the neutropenic murine pneumonia model. The pharmacokinetic properties of both drugs were linear over a dose range of 0.625 to 40 mg/kg of body weight. Protein binding was 30% for linezolid and 85% for TR-700. Mice were infected with one of 11 isolates of S. aureus, including MSSA and community- and hospital-acquired MRSA strains. Each drug was administered by oral-gastric gavage every 12 h (q12h). The dosing regimens ranged from 1.25 to 80 mg/kg/12 h for linezolid and 0.625 to 160 mg/kg/12 h for TR-701. At the start of therapy, mice had 6.24 ± 0.40 log(10) CFU/lungs, which increased to 7.92 ± 1.02 log(10) CFU/lungs in untreated animals over a 24-h period. A sigmoid maximum-effect (E(max)) model was used to determine the antimicrobial exposure associated with net stasis (static dose [SD]) and 1-log-unit reduction in organism relative to the burden at the start of therapy. The static dose pharmacodynamic targets for linezolid and TR-700 were nearly identical, at a free drug (non-protein-bound) area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) of 19 and 20, respectively. The 1-log-unit kill endpoints were also similar, at 46.1 for linezolid and 34.6 for TR-700. The exposure targets were also comparable for both MSSA and MRSA isolates. These dosing goals support further clinical trial examination of TR-701 in MSSA and MRSA pneumonia.

Advances of community-acquired methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major pathogens of the hospital infection.Its clinical features and drug-resisetance situations have always been concerned.But since the late 1990s,another class of MRSA has become a major concern worldwide as an emerging pathogen in the community.This new class of MRSA is called community-acquired MRSA (CA-MRSA).With the rapid development of the infection of CA-MRSA in 20 years,especially in the latest 3 years,CA-MRSA may be replacing the hospital-acquired MRSA strains(HA-MRSA) as one of the major pathogens in the hospital and the community as well.The characteristics of CA-MRSA are very different from those of HA-MRSA.This review summarizes the current studies of CA-MRSA on the epidemiology and the molecular characteristics. Key words: Community-acquired methicillin-resistant Staphylococcus aureus; Epidemiology; Gene

Transcriptional analysis of antibiotic resistance and virulence genes in multiresistant hospital-acquired MRSA

The staphylococcal chromosome cassette mec cannot solely explain the multiresistance phenotype or the relatively mild virulence profile of hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA). This study reports that several multiresistant HA-MRSA strains differently expressed genes that may support antibiotic resistance, modify the bacterial surface and influence the pathogenic process. Genes encoding efflux pumps (norA, arsB, emrB) and the macrolide resistance gene ermA were found to be commonly expressed by HA-MRSA strains, but not in the archetypal MRSA strain COL. At equivalent cell density, the agr system was considerably less activated in all MRSA strains (including COL) in comparison with a prototypic antibiotic-susceptible strain. These results are in contrast to those observed in recent community-acquired MRSA isolates and may partly explain how multiresistant HA-MRSA persist in the hospital setting.