Community-acquired Methicillin-resistant Staphylococcus Aureus Research Articles

Prevalence and Genetic Diversity of Staphylococcal Enterotoxin (-Like) Genes sey, selw, selx, selz, sel26 and sel27 in Community-Acquired Methicillin-Resistant Staphylococcus aureus

Staphylococcal enterotoxins (SEs) are virulence factors of Staphylococcus aureus associated with various toxic diseases due to their emetic and superantigenic activities. Although at least 27 SE(-like) genes have been identified in S. aureus to date, the newly identified SE(-like) genes have not yet been well characterized by their epidemiological features. In this study, the prevalence and genetic diversity of SE gene sey and SE-like genes selw, selx, selz, sel26, and sel27 were investigated for 624 clinical isolates of community-acquired methicillin-resistant S. aureus (CA-MRSA). The most prevalent SE(-like) gene was selw (92.9%), followed by selx (85.6%), sey (35.4%) and selz (5.6%), while sel26 and sel27 were not detected. Phylogenetically, sey, selw, selx, and selz were discriminated into 7, 10, 16, and 9 subtypes (groups), respectively. Among these subtypes, sey was the most conserved and showed the highest sequence identity (>98.8%), followed by selz and selx. The SE-like gene selw was the most divergent, and four out of ten genetic groups contained pseudogenes that may encode truncated product. Individual subtypes of SE(-like) genes were generally found in isolates with specific genotypes/lineages of S. aureus. This study revealed the putative ubiquity of selw and selx and the prevalence of sey and selz in some specific lineages (e.g., ST121) in CA-MRSA, suggesting a potential role of these newly described SEs(-like) in pathogenicity.

Discordance of vancomycin minimum inhibitory concentration for methicillin-resistant Staphylococcus aureus at 2μg/mL between Vitek II, E-test, and Broth Microdilution.

BackgroundVancomycin, the first line antibiotic for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, is often administered inappropriately when MIC is greater than 2 µg/mL, including ‘susceptible’ strains. This study assessed the discordance of vancomycin minimum inhibitory concentration (MIC) for methicillin-resistant Staphylococcus aureus (MRSA).MethodsIn total, 229 MRSA isolates from blood cultures collected between 2009 and 2015 at a tertiary hospital in Taiwan were examined. The MICs of vancomycin were measured using Vitek 2, E-test, and standard broth microdilution at the level of 2 µg/mL.ResultsThe geometric mean of the MICs of hospital-acquired MRSA was higher than that of community-acquired MRSA (P < 0.001), with the exact agreement rates (with broth microdilution) at 2 µg/mL being 53.6% in Vitek 2 and 86.7% in E-test. Overall, E-test (98.1%) had more categorical accordance than did Vitek 2 (94.0%; P = 0.026). Vitek 2 had a tendency to overestimate MRSA in high-MIC isolates, whereas E-test inclined underestimation in low-MIC isolates. Surprisingly, the discordance rates of MRSA vancomycin MICs were higher in hospital-acquired isolates (13.3%–17.0%) than in community-acquired isolates (6.2%–7.0%).ConclusionThe Infectious Diseases Society of America recommends the use of alternative antimicrobial agents when vancomycin MIC is ≥ 2 µg/mL; in this study, only 53.6% of the isolates tested using Vitek 2 showed a high MIC in the broth microdilution method. Accurate identification of the resistance profile is a key component of antimicrobial stewardship programs. Therefore, to reduce inappropriate antibiotic use and mitigate the emergence of resistant strains, we recommend using complementary tests such as E-test or Broth microdilution to verify the MIC before administering second-line antibiotics.Strengths(1) We compared the categorical agreement between different methods measuring MRSA MICs level. (2) Physicians should incorporate this information and consider a complementary test to verify the appropriateness of the decision of shifting vancomycin to second-line antibiotic treatment to improve patients’ prognosis. (3) MRSA-vancomycin MICs at a cutoff of 2 µg/mL obtained using Vitek II exhibited a higher sensitivity level and negative predictive value than those obtained using E-test in the prediction of categorical agreement with standard broth microdilution.Limitation(1) Our research was based on a single hospital-based study. (2) The MRSA strains in this study were stored for more than 12 months after isolation. (3) We did not collect information on clinical prognosis.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clones from Paraguayan children.

Staphylococcus aureus is considered one of the most important human pathogens, and its levels of resistance to methicillin have increased even in strains isolated from people without nosocomial risk factors. Molecular analysis is essential for understanding the patterns of dissemination. The objective of this study was to identify community-acquired methicillin-resistant S. aureus (CA-MRSA) clones that infected Paraguayan children patients in two periods of time. An observational, descriptive study was designed to determine the genetic variability of 115 isolates of CA-MRSA recovered from children who attended four reference centers in Paraguay between 2009-2010 and 2012-2013. The combined use of Pulsed Field Gel Electrophoresis (PFGE), Multi-Locus Sequencing Typing, Multi-Locus Variable Analysis (MLVA) and Spa typing techniques allowed the identification of two dominant clones: ST30-IV-t019 (77%) and ST5-IV-t311 (10%), and the establishment of the former as the leading cause of CA-MRSA infections in children during the study period. This is the first study that provides epidemiological information as well as microbiological and molecular characteristics of CA-MRSA isolates recovered from children from Asunción and the Central Department of Paraguay.

The Genomic Context for the Evolution and Transmission of Community-Associated Staphylococcus aureus ST59 Through the Food Chain

Sequence type 59 (ST59) is a predominant clonal lineage of community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) in Asia. Despite its increasing clinical relevance in China, the evolution and geographic expansion of ST59 has been relatively uncared for. Previous study has shown that ST59 was the predominant clone in food-related MRSA in China. This study compared the genomes of 87 clonal complex (CC) 59 S. aureus isolates sourced from food chain and infection cases to reconstruct the molecular evolution and geographical spread of ST59. Accordingly, three major sub-clades of ST59 were identified and these did not correlate with isolation source or location. Phylogenetic analysis estimated that ST59 in mainland China diverged from a most common recent ancestor around 1974, and most of the cases of cross-country transmission occurred between 1987 and 2000. Notably, two recent events of cross-country transmission through the food chain were observed, the isolates from these events diverged within relatively short time intervals. These isolates also showed high similarity in terms of their core genome, accessory genes, and antibiotic resistance patterns. These findings provide a valuable insight into the potential route of ST59 expansion in China and indicate a need for robust food chain surveillance to prevent the spread of this pathogen.

Panton Valentine Gene in both Community-acquired and Healthcare-acquired Methicillin Resistant Staphylococcus aureus Isolates from Ain Shams University Hospitals

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen that is associated with both hospital and community infections. Panton Valentine leukocidin (PVL) is an important virulence factor of S. aureus that is considered by many authors a marker of community acquired MRSA (CA-MRSA). Aim of the Work This study aimed to determine the prevalence of PVL genes among healthcare acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) and CA-MRSA isolates, and to test the hypothesis that PVL is a reliable marker of CA-MRSA isolates. Material and Methods This comparative cross-sectional study was done on fifteen community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and fifteen hospital acquired methicillin resistant Staphylococcus aureus (HA-MRSA), obtained from patients attending outpatient clinics, presenting with community-acquired pyogenic infections and patients with healthcare acquired pyogenic infections in Intensive Care Units (ICUs), during the period from May 2017 till February 2018. Clinical specimens included pus and different body fluids. Staphylococcus aureus was isolated and identified using conventional microbiological methods3. Isolates were then tested for methicillin resistance by culture on mannitol salt agar (MSA) with cefoxitin4. The presence of mecA and pvl genes in all MRSA isolates was subsequently detected by PCR5,6. Results Among 15 HA-MRSA isolates, mecA gene was positive in 40% (6/15) of isolates, while pvl gene was positive in 53.3% (8/15) of isolates. Among 15 CA-MRSA isolates, mecA gene was positive in 46.7% (7/15) of isolates, while pvl gene was positive in 26.7% (4/15) of isolates. Conclusion We conclude that pvl gene is not a sole genetic marker for diagnosis CA-MRSA, as there was no significant correlation between mecA that encodes for methicillin resistance and pvl genes among fifteen CA-MRSA isolates (P value =1).

Antibiotic use among twelve Canadian First Nations communities: a retrospective chart review of skin and soft tissue infections

BackgroundPrevious publications indicated an emerging issue with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), particularly skin and soft tissue infections (SSTIs), in Indigenous communities in Canada. The objectives of this analysis were to explore the prevalence of SSTIs due to CA-MRSA and patterns of antimicrobial use in the community setting.MethodsA retrospective chart review was conducted as part of an environmental scan to assess antibiotic prescriptions in 12 First Nations communities across five provinces in Canada including Alberta, Saskatchewan, Manitoba, Ontario, and Québec. Charts were randomly selected from nursing stations and patients who had accessed care in the previous 12 months and were ≥ 18 years were included in the review. Data was collected from September to December, 2013 on antibiotic prescriptions, including SSTIs, clinical symptoms, diagnostic information including presence of CA-MRSA infection, and treatment.ResultsA total of 372 charts were reviewed, 60 from Alberta, 70 from Saskatchewan, 120 from Manitoba, 100 from Ontario, and 22 from Québec. Among 372 patients, 224 (60.2%) patients had at least one antibiotic prescription in the previous 12 months and 569 prescriptions were written in total. The prevalence of SSTIs was estimated at 36.8% (137 cases of SSTIs in 372 charts reviewed). In 137 cases of SSTIs, 34 (24.8%) were purulent infections, and 55 (40.2%) were due to CA-MRSA.ConclusionsThis study has identified a high prevalence of antibiotic use and SSTIs due to CA-MRSA in remote and isolated Indigenous communities across Canada. This population is currently hard to reach and under-represented in standard surveillance system and randomized retrospective chart reviews can offer complimentary methodology for monitoring disease burden, treatment and prevention.

Protective activity of anti-lipoteichoic acid monoclonal antibody in single or combination therapies in methicillin-resistant Staphylococcus aureus-induced murine sepsis models

Previously, we generated and screened a panel of monoclonal antibodies (mAbs) against methicillin-resistant Staphylococcus aureus (MRSA) to identify protective mAbs in mouse infection models. One of these mAbs, ZBIA3H, bound to lipoteichoic acid (LTA) and exerted protective effects in a mouse sepsis model. To reinforce the ability of the mAb to protect against infection, combination therapies with the mAb and antibiotics need to be examined. Therefore, herein, we studied the efficacy of ZBIA3H (in combination or alone) in a mouse sepsis model. ZBIA3H improved the survival rate in the mouse models of sepsis induced by highly virulent or refractory S. aureus (community-acquired MRSA strain MW2, vancomycin-intermediate S. aureus strain Mu3, or vancomycin-resistant S. aureus strain VRS1). Furthermore, ZBIA3H remarkably improved the survival rate in combination with antimicrobial agents (vancomycin, daptomycin, or linezolid) in mouse sepsis models. From these results we conclude that anti-LTA mAb ZBIA3H or its humanized form is a promising mAb individually, or in combination with antibiotics, against clinical refractory infection of S. aureus.

Cysteine-Capped Hydrogels Incorporating Copper as Effective Antimicrobial Materials against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (S. aureus) (MRSA) has become an alarming threat to public health, and infected soft tissue. Antibiotics are commonly used to treat skin infection with MRSA, but the inappropriate use of antibiotics runs a considerable risk of generating resistant S. aureus. In this study, we created a cysteine-capped hydrogel able to absorb and release copper, an ion with the capability of suppressing the growth of USA300, a community-acquired MRSA. The results of analysis of Fourier transform infrared spectroscopy (FTIR) revealed the binding of copper to a cysteine-capped hydrogel. The topical application of a cysteine-capped hydrogel binding with copper on USA300-infected skin wounds in the dorsal skin of Institute of Cancer Research (ICR) mice significantly enhanced wound healing, hindered the growth of USA300, and reduced the production of pro-inflammatory macrophage inflammatory protein 2-alpha (MIP-2) cytokine. Our work demonstrates a newly designed hydrogel that conjugates a cysteine molecule for copper binding. The cysteine-capped hydrogel can potentially chelate various antimicrobial metals as a novel wound dressing.

Determination of Frequency and Nasal Carriage of Community-Acquired Methicillin-Resistant Staphylococcus aureus in Patients with Pyoderma

Objective: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have been increasingly reported in recent years, and they commonly cause skin and skin-related structure infections. The aim of this study was to investigate CA-MRSA frequency and nasal carriage in patients with pyoderma. Methods: Between November 2011 and August 2013, we aimed to investigate the frequency of […]

Prevalence of Community Acquired Methicillin Resistant Staphylococcus aureus Nasal Carriage among Children of Consultation: Experience of a Moroccan University Hospital

Background: The carriage of Staphylocoque aureus, including methicillin-resistant S. aureus (MRSA), is a significant risk factor for subsequent staphylococcal infection. The nares are the most consistent sites of colonization. The objective of this study was to determine prevalence for community acquired methicillin-resistant S. aureus (CA-MRSA) nasal carriage among a pediatric population as well as to find out antibiotic susceptibilities of isolated strains. Patients and methods: We conducted a prospective study from June 2017 to June 2018 on 300 children, who consulted in the different pediatric specialties of Mohamed VI University Hospital of Marrakesh. Nasal swabs were collected from all the consultant children. The identification of nasal carriage of SA was performed in the microbiology laboratory of Mohamed VI University Hospital. Results: Staphylocoque aureus was isolated from the nares in 49 (16.3%) children, two (4%) isolates were classified as CA-MRSA. The mean children age was 75, 14 months (p=0.05), a male predominance was noticed. The majority of SA carriers were from urban areas, it was noted a high carriage in living patients with five or more people (p=0.024). Antimicrobial susceptibility testing of MRSA stains expressed a 100% resistance to cotrimoxazole, fusidic acid and sensitivity to all other antibiotics. Conclusion: This study highlights the potential for community MRSA acquisition in our context. These strains, which were initially sensitive to most of antibiotics, begin to become increasingly resistant to nobetalactam antibiotics. This requires continuous monitoring to clarify the factors of antimicrobial resistance and to prevent further spread of community MRSA.

Community-Acquired MRSA Bacteraemia in a Healthy 6-Year-Old Female

Community-Acquired MRSA Bacteraemia in a Healthy 6-Year-Old Female

One Health Approach Reveals the Absence of Methicillin-Resistant Staphylococcus aureus in Autochthonous Cattle and Their Environments

Antimicrobial resistance represents one of the greatest challenges of the twenty-first century, and it is globally recognized that addressing this problem requires a concerted One Health approach involving humans, animals, and the environment. Methicillin-resistant Staphylococcus aureus (MRSA) currently represents a global burden; it is resistant to almost all beta-lactams and some MRSA strains are highly multiresistant. S. aureus infection in cattle results in major economic losses in the food industry. Moreover, cases of livestock-associated MRSA strains responsible for invasive life-threatening infections have been reported among human patients in contact with infected or colonized animals. The autochthonous Maronesa cattle breed is a threatened rustic traditional Portuguese breed of mountain cattle of high importance for the Vila Real region. It has been used for centuries as motive power in all kinds of agricultural work and also for meat production, which is its current dominant use and the main source of economic value, being the Maronesa meat commercialized with PDO - Protected Designation of Origin. This study aimed to determine the prevalence and transmission of MRSA in cattle of the Maronesa breed, through a concerted One Health approach comprising human, water, and soil samples of the animals’ handlers and environments. In a total of 195, 63, 40, and 43 cattle, human, water, and soil samples screened in selective ORSAB media supplemented with 2 mg/L oxacillin; only one human sample harbored a MRSA isolate which was ascribed to spa-type t9413 and to ST30, one of the most common genetic lineages associated with community-acquired MRSA. Considering the increasing reports of MRSA isolation from cattle and handlers in Europe, the absence of this major human and animal pathogen in Maronesa cattle and their production systems represents a serendipitous result, valuing this important autochthonous breed. To our knowledge, this is the first study to determine MRSA prevalence and transmission in Maronesa cattle. Through a concerted One Health approach, this study revealed that the Maronesa cattle and their surrounding environments do not represent reservoirs for Methicillin-resistant Staphylococcus aureus.

AN REVIEW METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS (MRSA): CHARACTERIZATION, PREVALENCE AND ANTIBIOTIC REACTIONS ON HUMAN IN INDIA

Introduction: Community acquired MRSA (CA-MRSA) has been increasingly examined from India(4). A network of microbiology labs (Indian Organization for Surveillance of Antimicrobial Resistance - INSAR) at premier medical colleges and hospitals in India was assembled with support from the World Health Organization (figure). Prevalence of Methicillin Resistant Staphylococcus Aureus: A study displays an alarmingly high incidence of MRSA corruption in the BHU hospital. The prevalence rate is established to be 54.8%, which is much higher than most of the results where it ranged between 20% to 32.8%.(17),(18) The only report which has given somewhat similar result i.e. 51.6% is from LN Hospital, New Delhi.(19) Further, a study from Indore has shown a grow in MRSA prevalence from 12% in 1992 to 80.89% in 1999.(20) Modes of transmission and virulence factors: Due to its capability to colonize a wide range of strains (all mammals including rodents and lagomorphs), S. aureus can easily be transmitted from one species to another; from humans to animals and reverse. Staphylococcal infections are zoonotic in nature. Antibiotic Reaction on Human: The sensitivity patterns of divided to different antibiotic discs were read by measuring the diameter of area of inhibition in millimeter as per the chart provided by manufacturer and classified as Sensitive, Intermediate and Resistant based on CLSI guidelines.(8)&#x0D; Keywords: Antimicrobial, Bugs, Lagomorphs, MRSA, Rodent, Sensitivity, Staphylococcus.

Extracorporeal cardiopulmonary resuscitation for aortic rupture secondary to purulent pericarditis

Background: Extracorporeal Cardiopulmonary Resuscitation (ECPR) has been increasingly usedfor failed conventional CPR. Successful use in sudden major vessel rupture hasn't been reported. Cases of community-acquired methicillin-resistant staphylococcus aureus (CA-MRSA) pericarditis associated with major vessel rupture however are limited in number1 with a reported mortality of 20–30%.2 Here we present a case of CA-MRSA pericarditis that was complicated by aortic rupture in which ECPR was successfully utilized. Methods: A four-year-old boy presented with fever, abdominal pain and vomiting for one day. He had a fall from a tricycle with potential abdominal injury the day before and had a small gluteal abscess present for four days. Examination showed slight tachycardia, mild tachypnea and low-grade fever. CBC showed neutrophilic leukocytosis. Initial chest x-ray, electrocardiogram, and abdominal tomography scan were normal. He was managed with analgesics and covered with ceftriaxone. Chest CT done on the third day due to tachypneashowed pericardial and bilateral pleural effusions. Echocardiography showed a large pericardial effusion with a collapsing atrium, indicating tamponade. Emergency pericardiocentesis retrieved 120 ml of serosanguinous fluid. A pigtail catheter was left in-situ. Intravenous vancomycin was added to the antibiotic coverage. Pericardial fluid culture grew MRSA. He showed clinical improvement, and inflammatory markers showed progressive decrease. Pericardial drain was removed after five days as the drained fluid became minimal. Subsequent echocardiograms showed only debris in the pericardial space.Five days later while looking well, he coughed, desaturated, and became hemodynamically unstable. He was resuscitated for 55 minutes, during which he mostly had pulseless electrical activity. Bedside sternotomy was done during resuscitation to initiate central ECMO as part of ECPR. The pericardial sac was bulging, and when opened, around 500 ml of fresh blood with clots came out. Blood jets were coming from the ascending aorta which was found ruptured and covered with a thick layer of organized pus. Pus was removed from around the superior vena cava, right ventricle and ascending aorta, and the aorta was sutured.The patient was connected to femoral VA ECMO as the aortic wall was very friable. Results/outcome: The patient was decannulated from ECMO after 3 days and discharged from hospital after 2 months. At discharge, he was alert, communicating and had generalized weakness. MRI brain showed hypoxic ischemic changes. Conclusion: This is the first pericarditis case reported to develop aortic rupture, and the first to survive after a pericarditis-associated major vessel rupture, with utilization of ECPR and timely surgical repair. One case ofMRSA purulent pericarditiswith pulmonary trunk rupture was reported in a 68 year old woman who expired due to massive bleeding and difficulty of surgical repair.3 Although pericardiectomy should be considered from the outset in the management of purulent pericarditis,4 surgical intervention was not considered initially as the aspirated pericardial fluid was visually serosanguinous andsubsequent echocardiograms didn't show reaccumulation. Prior to admission, there was a small gluteal abscess, which probably served as the portal of entry for the MRSA but was dry at the time of admission and was not sampled.

Characterization of a community-acquired methicillin-resistant sequence type 338 Staphylococcus aureus strain containing a staphylococcal cassette chromosome mec type VT

ObjectivesTo determine the molecular characteristics of a sequence type 338 community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) strain and the relationship among MRSA strains from various lineages and areas. MethodsWhole-genome sequencing, genomic comparison, antimicrobial susceptibility testing, and hemolysis analysis were performed to identify the resistance determinants and virulence factors of strain ZY05 and the relationships among CC59 clones. ResultsMRSA strain ZY05 was resistant to tetracycline, erythromycin, and clindamycin, and the resistance genes erm(B) and tet(K) were detected in the genome. ZY05 harbors the genomic islands νSaα, νSaβ, νSaγ, and ΦSa2, the pathogenicity island νSa1, and virulence factors such as Panton–Valentine leukocidin, phenol-soluble modulins, alpha-hemolysin, enterotoxin B, enterotoxin K, and enterotoxin Q, which are the same as those present in ST59 strains. In addition, the virulence potential of ST338 did not differ from that of ST59. This strain contains the staphylococcal cassette chromosome mec (SCCmec) type VT, a distinct SCCmec type previously reported from Taiwan. The results of core genome multilocus sequence typing (cgMLST) analysis showed that the gene distances between ST59 and ST338 were close among CC59 isolates, while strains from Taiwan were identical to isolates from the Chinese mainland with respect to these two sequence types. ConclusionsThe ST338 strain ZY05, which has a close genetic relationship to ST59 strains, is multidrug-resistant and highly virulent. Strains of two identical lineages, ST59 and ST338, from Taiwan and the Chinese mainland may have the same genetic background.

Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus nasal carriage in the West of Iran: a population-based cross-sectional study

BackgroundSeveral reports designate the recent increase in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) nasal carriage. Because of the scanty information regarding the nasal carriage sate of MRSA in the west of Iran, the purpose of the present study was to determine the frequency of CA-MRSA in Sanandaj city.MethodsSwabs collected from anterior nares of 600 volunteers were analyzed for the presence of S. aureus. The isolates were further investigated for methicillin resistance by using the cefoxitin disk diffusion test, followed by PCR-amplification of the mecA gene. SCCmec types and the presence of the Panton-Valentine Leukocidin (pvl) encoding genes were determined through PCR. Finally, the antimicrobial susceptibility of the isolates was determined by the agar diffusion method.ResultsNasal screening identified 181 S. aureus, of which 55 isolates were MRSA. SCCmec types IV and V were detected in MRSA at frequencies of 80 and 20%, respectively. The overall frequency of pvl genes among the MRSA isolates was 14.54%. MRSA isolates were highly susceptible (98.18%) to mupirocin, gentamicin, and fusidic acid.ConclusionsThe high prevalence of CA-MRSA carriage in the population could pose a serious public health concern for the region. Additionally, advent of drug-resistant pvl-positive strains demands continuous surveillance on the colonization state of CA-MRSA in order to prevent dissemination of the bacterium in the community.

Comparing methods to estimate incremental inpatient costs and length of stay due to methicillin-resistant Staphylococcus aureus in Alberta, Canada

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic bacterial organism resistant to first line antibiotics. Acquisition of MRSA is often classified as either healthcare-associated or community-acquired. It has been shown that both healthcare-associated and community-acquired infections contribute to the spread of MRSA within healthcare facilities. The objective of this study was to estimate the incremental inpatient cost and length of stay for individuals colonized or infected with MRSA. Common analytical methods were compared to ensure the quality of the estimate generated. This study was performed at Alberta Ministry of Health (Edmonton, Alberta), with access to clinical MRSA data collected at two Edmonton hospitals, and ministerial administrative data holdings.MethodsA retrospective cohort study of patients with MRSA was identified using a provincial infection prevention and control database. A coarsened exact matching algorithm, and two regression models (semilogarithmic ordinary least squares model and log linked generalized linear model) were evaluated. A MRSA-free cohort from the same facilities and care units was identified for the matched method; all records were used for the regression models. Records span from January 1, 2011 to December 31, 2015, for individuals 18 or older at discharge.ResultsOf the models evaluated, the generalized linear model was found to perform the best. Based on this model, the incremental inpatient costs associated with hospital-acquired cases were the most costly at $31,686 (14,169 – 60,158) and $47,016 (23,125 – 86,332) for colonization and infection, respectively. Community-acquired MRSA cases also represent a significant burden, with incremental inpatient costs of $7397 (2924 – 13,180) and $14,847 (8445 – 23,207) for colonization and infection, respectively. All costs are adjusted to 2016 Canadian dollars. Incremental length of stay followed a similar pattern, where hospital-acquired infections had the longest incremental stays of 35.2 (16.3–69.5) days and community-acquired colonization had the shortest incremental stays of 3.0 (0.6–6.3) days.ConclusionsMRSA, and in particular, hospital-acquired MRSA, places a significant but preventable cost burden on the Alberta healthcare system. Estimates of cost and length of stay varied by the method of analysis and source of infection, highlighting the importance of selecting the most appropriate method.

613. Suppression of Daptomycin Resistance Development in Staphylococcus aureus Is a Class Effect of β-Lactams and Is Independent of Daptomycin–β Lactam Synergy

BackgroundPrevious studies demonstrate that adding oxacillin during daptomycin (DAP) exposure can prevent DAP resistance development in community-acquired (ST8/USA300) MRSA, presumably by preventing mprF mutation. Hospital-acquired strains, such as MRSA sequence types 5 and 239, typically have higher β-lactam (BL) minimum inhibitory concentrations (MICs) than their community-acquired counterparts and are often less toxigenic, more multidrug-resistant and more refractory to primary antistaphylococcal therapies. It is unknown whether DAP resistance prevention occurs in hospital-acquired MRSA lineages or if augmenting DAP therapy with BL antibiotics other than oxacillin would prevent DAP resistance development.MethodsMRSA ST5/USA100 (D592) and ST239 (JKD6004) differ in the degree to which BL enhances DAP activity. D592 and JKD6004 were passaged in escalating concentrations of DAP in a stepwise fashion in vitro as described previously. Following 28 days of serial passage all replicates were passaged twice on mannitol-salt agar and tested for DAP MIC by Etest. Parallel passages were performed in media supplemented with BL antibiotics. Between-group differences in DAP MIC suppression effectiveness among individual BLs compared with nafcillin was evaluated using Kruskal–Wallis rank-sum testing with Holm-adjusted post-hoc Dunn testing.ResultsPassage of D592 or JKD6004 in DAP resulted in highly DAP-resistant isolates (median ≥256 mg/L, IQR [96,256]). In contrast, when passages were performed in the presence of DAP+BL, DAP resistance development was suppressed. No between-group differences in DAP MIC suppression effectiveness were observed among individual BLs compared with nafcillin. Highly DAP-resistant isolates demonstrated variable collateral susceptibility to BL monotherapy but were frequently susceptible to combination antibiotic exposure.ConclusionAddition of β-lactams to DAP can prevent DAP resistance development in vitro in ST5/USA100 and ST239 MRSA, consistent with findings in ST8/USA300 lineages. Furthermore, this ability appears to be a class effect of β-lactam antibiotics and is independent of the extent of DAP-BL synergy. This provides evidence to support the use of BL combination therapy without regard to staphylococcal lineage or specific BL used.Disclosures All authors: No reported disclosures.

1523. Clinical Epidemiology of Children with Orbital Cellulitis

BackgroundThe microbiology of pathogens causing orbital cellulitis in children is evolving over time, with studies from around 10 years ago describing MRSA as responsible for anywhere from 0 to 13% of cases of orbital cellulitis. However, the prevalence of community-acquired MRSA infections has declined over the past decade. A current understanding of the bacteria most commonly found to be responsible for orbital cellulitis would be important to inform the empiric antibiotic regimens for cases of orbital cellulitis in which no microbiologic data are available.MethodsThis is a single-center retrospective cohort study of children ≤18 years hospitalized with orbital cellulitis at Children’s National Medical Center between January 1, 2017 and July 31, 2018. We excluded children with immunocompromising conditions, cystic fibrosis, underlying craniofacial abnormality, or recent craniofacial or otolaryngologic surgery. Baseline clinical characteristics, microbiologic data, clinical outcomes, and antibiotic treatment data were abstracted through structured chart review and summarized with descriptive statistics.ResultsWe identified 68 children that met inclusion criteria, with an average age of 8.2 years; 66.2% were male, 48.5% were African American, and 14.7% were Hispanic. Most (67.6%) had no underlying medical problems, 14.7% had asthma, and 22.1% had allergic rhinitis. The median duration of symptoms prior to presentation was 4 days. An abscess or phlegmon was identified in 41 of the 68 (60.3%). Three patients (4.4%) developed intracranial complications. About one-quarter (27.9%) of all patients in the cohort underwent surgical drainage. The most commonly identified pathogens were viridans group streptococci (7/19, 36.8%), followed by Staphylococcus aureus (4/19, 21.1%). Anti-MRSA therapy was provided empirically in almost all (95.6%) of patients.ConclusionOne-quarter of all patients hospitalized for orbital cellulitis underwent surgical drainage, and viridans group streptococci and S. aureus were the most commonly isolated pathogens. While MRSA was isolated in only one patient (5.2%), almost all received empiric anti-MRSA therapy. Disclosures All authors: No reported disclosures.

Enantiomeric glycosylated cationic block co-beta-peptides eradicate Staphylococcus aureus biofilms and antibiotic-tolerant persisters

The treatment of bacterial infections is hindered by the presence of biofilms and metabolically inactive persisters. Here, we report the synthesis of an enantiomeric block co-beta-peptide, poly(amido-D-glucose)-block-poly(beta-L-lysine), with high yield and purity by one-shot one-pot anionic-ring opening (co)polymerization. The co-beta-peptide is bactericidal against methicillin-resistant Staphylococcus aureus (MRSA), including replicating, biofilm and persister bacterial cells, and also disperses biofilm biomass. It is active towards community-acquired and hospital-associated MRSA strains which are resistant to multiple drugs including vancomycin and daptomycin. Its antibacterial activity is superior to that of vancomycin in MRSA mouse and human ex vivo skin infection models, with no acute in vivo toxicity in repeated dosing in mice at above therapeutic levels. The copolymer displays bacteria-activated surfactant-like properties, resulting from contact with the bacterial envelope. Our results indicate that this class of non-toxic molecule, effective against different bacterial sub-populations, has promising potential for the treatment of S. aureus infections.