Treatment Of Methicillin-resistant Staphylococcus Aureus Research Articles

Prevalence and Therapies of Antibiotic-Resistance in Staphylococcus aureus.

Infectious diseases are the second most important cause of human death worldwide; Staphylococcus aureus (S. aureus) is a very common human pathogenic microorganism that can trigger a variety of infectious diseases, such as skin and soft tissue infections, endocarditis, osteomyelitis, bacteremia, and lethal pneumonia. Moreover, according to the sensitivity to antibiotic drugs, S. aureus can be divided into methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). In recent decades, due to the evolution of bacteria and the abuse of antibiotics, the drug resistance of S. aureus has gradually increased, the infection rate of MRSA has increased worldwide, and the clinical anti-infective treatment for MRSA has become more difficult. Accumulating evidence has demonstrated that the resistance mechanisms of S. aureus are very complex, especially for MRSA, which is resistant to many kinds of antibiotics. Therefore, understanding the drug resistance of MRSA in a timely manner and elucidating its drug resistance mechanism at the molecular level are of great significance for the treatment of S. aureus infection. A large number of researchers believe that analyzing the molecular characteristics of S. aureus can help provide a basis for designing effective prevention and treatment measures against hospital infections caused by S. aureus and further monitor the evolution of S. aureus. This paper reviews the research status of MSSA and MRSA, the detailed mechanisms of the intrinsic antibiotic resistance and the acquired antibiotic resistance, the advanced research on anti-MRSA antibiotics and novel therapeutic strategies for MRSA treatment.

Prevalence, molecular characteristics and antimicrobial susceptibility patterns of MRSA in hospitalized and nonhospitalized patients in Barbados.

The epidemiology and clonality of methicillin-resistant Staphylococcus aureus (MRSA) has not been investigated, as not much research or surveillance has been undertaken to identify and characterize the circulating MRSA strains in Barbados. Prevalence rates, molecular characteristics and antimicrobial susceptibility pattern of MRSA infections in hospitalized and nonhospitalized patients were investigated. A total of 293 isolates were included in the study, with 100 from the hospital and 193 from the public health laboratory. Isolates were collected over a period of 1 (2015–2016) and 3 years (2013–2016) respectively. MRSA was identified using standard microbiologic techniques and was further analysed by multiplex PCR for the presence of the spa, mec gene complex typing and PVL genes (lukS-PV and lukF-PV). A prevalence rate of 19.7% was calculated for those hospitalized. All hospital isolates were sensitive to vancomycin, rifampin, linezolid and cotrimoxazole (trimethoprim/sulfamethoxazole), whilst 82% were sensitive to clindamycin. The PVL gene was detected in 76% of hospital isolates. In the community isolates, resistance was observed in erythromycin (100%), ciprofloxacin (97.4%), clindamycin (13%) and cotrimoxazole (5.7%). There was no resistance to vancomycin. The PVL gene was detected in 97.9% of the isolates, the mecA gene in only 2.1% and the mecC gene in 0%. Most MRSA isolates were community acquired in both settings, and the antimicrobial susceptibility profile was similar, suggesting transmission of community-associated MRSA into the hospital environment. Further harmonization of antimicrobial policy for the treatment of MRSA (and by extension other pathogens) should be implemented to quell ongoing transmission. We found that 93.4% of MRSA in Barbados treated in the primary healthcare system were sensitive to cotrimoxazole. By typing MRSA isolates and drawing interferences on transmission on the basis of genetic relatedness, transmission pathways may be tracked. Further studies must be performed for this high level of comprehensiveness so that with the surveillance of MRSA, effective strategies may be developed to prevent or limit transmission.

Role of linezolid combination therapy for serious infections: review of the current evidence.

As long-standing clinical problems, a series of complicated infections are more difficult to treat due to the development of antibiotic resistance, especially caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis). Moreover, the treatment options available to against these infections are also becoming increasingly limited. Linezolid is the first synthetic oxazolidinone antibiotic with a unique mechanism of action, and its efficacy against Gram-positive bacteria has been clearly demonstrated. However, the limitations of linezolid alone for the treatment of these complicated infections have been reported in the recent years. Combination therapy may be a good approach to enhance efficacy and prevent the development of resistance. In this review, the results of multiple linezolid combination therapies from in vitro, animal studies, and clinical cases for the treatment of MRSA, VRE, and multidrug-resistant M. tuberculosis strains will be discussed, and thus provide more relevant information for clinician in clinical practice.

Potent trifluoromethoxy, trifluoromethylsulfonyl, trifluoromethylthio and pentafluorosulfanyl containing (1,3,4-oxadiazol-2-yl)benzamides against drug-resistant Gram-positive bacteria.

According to the Centers for Disease Control and Prevention (CDC), methicillin-resistant Staphylococcus aureus (MRSA) affects about 80 000 patients in the US annually and directly causes about 11 000 deaths. Therefore, despite the fact that there are several drugs available for the treatment of MRSA, there is a need for new chemical entities. We previously reported that 1,3,4-oxadiazolyl sulfonamide F6 was bacteriostatic and inhibited MRSA strains with a minimum inhibitory concentration (MIC) of 2 μg mL-1. Here, we report the discovery of trifluoromethoxy (OCF3), trifluoromethylsulfonyl (SO2CF3), trifluoromethylthio (SCF3) and pentafluorosulfanyl (SF5) containing (1,3,4-oxadiazol-2-yl)benzamides exhibiting potent antibacterial activities against MRSA [MIC values as low as 0.06 μg mL-1 against linezolid-resistant S. aureus (NRS 119)]. Interestingly, whereas the OCF3 and SO2CF3 containing oxadiazoles were bacteriostatic, the SCF3 and SF5 containing oxadiazoles were bactericidal. They exhibited a wide spectrum of activities against an extensive panel of Gram-positive bacterial strains, including MRSA, vancomycin-resistant Staphylococcus aureus (VRSA), vancomycin-resistant enterococcus (VRE) and methicillin-resistant or cephalosporin-resistant Streptococcus pneumoniae. Furthermore, compounds 6 and 12 outperformed vancomycin in clearing intracellular MRSA in infected macrophages. Moreover, the tested compounds behaved synergistically or additively with antibiotics used for the treatment of MRSA infections.

Antimicrobial Resistance Patterns and Plasmid Profiles of Methicillin Resistant Staphylococcus aureus Isolated from Clinical Samples

Methicillin-resistant Staphylococcus aureus (MRSA), showing resistance to several antibiotics is a global health problem associated with considerable mortality and morbidity. Antibiotic susceptibility test is a commonly used method to characterize MRSA in epidemiologic studies. Additionally, plasmid profile has been reported to be useful in tracing the epidemiology of antibiotic resistance. This research was conducted to determine the antimicrobial resistance patterns and plasmid profiles of MRSA isolated from clinical samples at KIST Medical College, Imadol, Kathmandu, Nepal. All the clinical specimens sent to the laboratory were processed by standard microbiological techniques and antibiotic susceptibility testing was done by the modified Kirby Bauer disc diffusion method. Further, plasmid profiling was done by Alkaline-lysis method. A total of 27 (38.02%) MRSA were isolated from 71 S. aureus positive samples. MRSA showed the highest resistance towards penicillin (92.60%) and ampicillin (92.60%). In contrast, high levels of sensitivity were shown towards vancomycin (85.19%) and tetracycline (85.19%). Out of 27 MRSA positive samples, single plasmids were isolated from only 6 (22.22%) MRSA isolates. Antibiograms alone are inadequate to accomplish the characterization of MRSA during epidemiological studies. However, plasmid profile analysis in conjunction with the antibiotic susceptibility pattern is valuable in the epidemiological investigation of MRSA, and for reducing MRSA prevalence and treatment cost.

The bactericidal effect of liposomal vancomycin as a topical combating system against Methicillin-resistant Staphylococcus aureus skin wound infection in mice.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of skin infections and treatment is difficult due to its resistance to the most of antibiotics. Although vancomycin is often considered as an antibacterial agent of choice for the treatment of MRSA, its use is limited because of the high side effects. One solution is using liposomal formulation for local drug delivery. The aim of this study was to determine in vitro and in vivo efficacies of liposomal vancomycin as topical use. Methods: To prepare liposomal vancomycin, the ammonium sulfate gradient using remote loading and freeze-thaw methods was applied. Then, synthesized nanoliposomes were evaluated in terms of particle size, morphology, stability, and encapsulation efficiency. Minimum inhibitory concentration (MIC) of synthesized nanoliposome against MRSA was detected. The cytotoxicity of synthesized nanoliposome was evaluated using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Finally, the topical antibacterial activity of each formulation was tested against MRSA-infected skin wound model in mice. Results: High encapsulation efficiency was achieved for all synthesized nanoliposomes. The results of in vitro and in vivo showed that liposomal vancomycin was more effective than free vancomycin. Also, synthesized nanoliposome showed no cytotoxicity on human epidermoid cell line. Conclusion: The results showed that synthesized nanoliposome could be applied as a great topical antimicrobial construct for treatment of MRSA skin infections.

Lipidated α/Sulfono-α-AA heterogeneous peptides as antimicrobial agents for MRSA

Though antibiotics have been used for decades to treat bacterial infections, there is a great need for new treatment methods. Bacteria are becoming resistant to conventional antibiotics, as is the case with Methicillin resistant Staphylococcus aureus (MRSA). Herein we report the design of a series of lipidated α/Sulfono-α-AA heterogeneous peptides as mimics for Host Defense Peptides (HDPs). Utilizing fluorescence microscopy and depolarization techniques, our compounds demonstrate the ability to kill Gram-positive bacteria through cell membrane disruption. This mechanism of action makes it difficult for bacteria to develop resistance. Further time kill studies and hemolytic assays have also proven these compounds to be efficient in their ability to eradicate bacteria cells while remaining non-toxic to human red blood cells. This new class of peptidomimetics shows promise for the future antibiotic treatment of MRSA.

Enhancement in Site-Specific Delivery of Carvacrol against Methicillin Resistant Staphylococcus aureus Induced Skin Infections Using Enzyme Responsive Nanoparticles: A Proof of Concept Study.

Methicillin resistant Staphylococcus aureus (MRSA) induced skin infections have become a challenging problem due to the escalating antibiotic resistance. Carvacrol (CAR) has been reported to be effective against MRSA. However, due to its characteristics, CAR exhibits low skin retention. In this study, CAR was formulated into site-specific nanoparticle (NPs) delivery system using poly(ε-caprolactone) (PCL), following incorporation into a hydrogel matrix to facilitate dermal delivery. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacterial lipase, highlighting its potential for differential delivery. Moreover, encapsulation of CAR in PCL NPs resulted in a two-fold increase in its anti-MRSA activity. Dermatokinetic studies revealed that the NPs loaded hydrogel was able to enhance skin retention of CAR after 24 h (83.29 ± 3.15%), compared to free CAR-loaded hydrogel (0.85 ± 0.14%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo skin infection model. Hence, these findings have proven the concept that the loading of CAR into a responsive NPs system can lead to sustained antimicrobial effect at the desired site, and may provide a novel effective approach for treatment of MRSA induced skin infections. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.

Potential Impact of Hospital-acquired Pneumonia Guidelines on Empiric Antibiotics. An Evaluation of 113 Veterans Affairs Medical Centers.

Rationale: The 2016 guidelines for hospital-acquired pneumonia (HAP) suggest applying a universal antibiogram resistance threshold in addition to patient criteria to determine empiric coverage. The impact of these recommendations is unknown.Objectives:1) Describe national antibiotic use and microbiology patterns for HAP among patients with noninfectious admissions, 2) measure the predictive performance of the antibiogram threshold and risk factors, and 3) estimate the change in practice with guideline implementation.Methods: We conducted a retrospective analysis of all hospitalizations without initial infection but with secondary pneumonia diagnoses at Veterans Affairs Medical Centers between October 1, 2012, and September 30, 2015. For each hospitalization we extracted: presence of methicillin-resistant Staphylococcus aureus (MRSA) and resistant gram-negative rods (R-GNR) in cultures, anti-MRSA and antipseudomonal antimicrobial administration, and facility-level prevalence of MRSA and R-GNR. We calculated the percentage of hospitalizations with resistant organisms, broad-spectrum antibiotics, and the predictive performance of patient characteristics and prevalence thresholds for MRSA.Results: Among 3,562 cases, 5.17% were positive for MRSA and 2.30% for R-GNR. The recommended MRSA prevalence threshold was 100.00% sensitive (95% confidence interval [CI], 98.02-100.00%) and 0.03% specific (95% CI, 0.00-0.16%) for MRSA-positive culture, leading to overtreatment of 94.81% (95% CI, 94.02-95.50%) of patients. Pressor order (odds ratio [OR], 3.89; 95% CI, 1.17-12.91) and intravenous antibiotics within the past 90 days (OR, 1.98; 95% CI, 1.03-3.81) were associated with MRSA. Mechanical ventilation was associated with R-GNR (OR, 4.37; 95% CI, 1.52-12.57).Conclusions: The guideline-recommended antibiogram threshold and characteristics did not improve prediction of MRSA or R-GNR and would have led to an increase in MRSA treatment.

In vitro and in vivo evaluation of linezolid loaded electrospun PLGA and PLGA/PCL fiber mats for prophylaxis and treatment of MRSA induced prosthetic infections.

In this study, it was aimed to formulate linezolid loaded electrospun PLGA and PCL fiber mats doing controlled drug release, to be used in the treatment and prophylaxis of the prosthesis related infections. The effect of PLGA concentration, PLGA to PCL ratio and the amount of linezolid on the fiber and mat properties were examined. Fiber diameter has been shown to increase with increasing amount of PLGA and linezolid. Increase in PLGA amount resulted in reduced linezolid release, whereas increase in linezolid amount resulted in increased drug release. All PLGA fiber mats have shown to have favorable encapsulation efficiency (≥73%) and mechanical properties. Encapsulation efficiency and the mechanical properties deteriorated with the addition of PCL to the formulations. PLGA fiber mats have shown a biphasic controlled release and in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), pattern up to one month. The formulation selected as the optimum has been evaluated in vivo on the infected rats, which had prosthetic implantation after bone fracture. Consequently, it has been demonstrated microbiologically and histopathologically that a more efficient therapy and prophylaxis have been achieved with a 37-fold lower dose of linezolid.

Effect of UV-C light or hydrogen peroxide wipes on the inactivation of methicillin-resistant Staphylococcus aureus, Clostridium difficile spores and norovirus surrogate.

The current study aimed to assess the potential of a new high dose ultraviolet (UV) disinfection device to inactivate methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile and a norovirus surrogate on handheld mobile devices, and to compare the efficacy of the UV-C device to hydrogen peroxide disinfection wipes. Suspensions of MRSA, C. difficile spores and a surrogate for norovirus (MS2) were inoculated onto glass or plastic coupons, with or without organic contamination and were exposed to continuous UV-C light for 15-60s (165-646mJcm-2 ) in a self-contained UV-C chamber or treated with hydrogen peroxide wipes. Increasing the UV-C dose from 310 to 650mJcm-2 did not result in greater levels of inactivation. UV-C light inactivated all three micro-organisms, in the absence of organic contamination, by >2·9 log. Treatment of MRSA, C. difficile spores or MS2, in the presence of organic contamination, with UV-C light (310-646mJcm-2 ) resulted in 2·3-3·7 log reductions. Treatment of MRSA with UV-C light provided levels of inactivation comparable to treatment with hydrogen peroxide wipes used following the manufacturer's instructions. UV-C light and hydrogen peroxide wipes had strong antimicrobial activity against MRSA, C. difficile spores and a norovirus surrogate, in the presence or absence of organic contamination. Chemical disinfection wipes are widely used in healthcare facilities, but they are not recommended for use on handheld mobile devices which may harbour pathogenic micro-organisms. The powerful bactericidal, sporicidal and virucidal activity of this high dose UV-C light device, shows that this technology is a promising alternative to chemical disinfectants, particularly for control of MRSA.

Nano MOF Entrapping Hydrophobic Photosensitizer for Dual-Stimuli-Responsive Unprecedented Therapeutic Action against Drug-Resistant Bacteria

Multidrug resistance (MDR) of bacteria is a major threat to public health globally and its unprecedented increase calls for immediate alternative medical strategies. Antimicrobial photodynamic therapy (aPDT) offers alternative modalities to combat the growing MDR typically by means of targeted cellular internalization of a photosensitizer (PS) capable of producing photoinduced reactive oxygen species (ROS). However, aPDT is severely limited by the self-aggregation behavior and hydrophobicity of PS molecules, which significantly curbs its viability for clinical application. The present study reports the use of modified nanoscale metal-organic frameworks (NMOFs) encapsulating a hydrophobic PS drug squaraine (SQ) to enhance aPDT efficacy against drug-resistant planktonic bacteria and its biofilm for the first time. Zeolitic imidazolate framework (ZIF-8) NMOF nanocrystals are attached postsynthetically with SQ (designated as ZIF8-SQ) and the resultant drug-doped NMOF is characterized by TEM, FESEM, PXRD, Raman spectroscopy, UV-vis spectroscopy, and steady-state and time-resolved fluorescence techniques. The microporous structures of ZIF-8 behave as molecular cages ceasing the self-aggregation of hydrophobic SQ. In addition, the formulated ZIF8-SQ produces cytotoxic ROS under red-light irradiation (650 nm) in a pH sensitive way primarily due to molecular level interaction and charge separation between ZIF-8 and SQ depicting a dual-stimuli-responsive nature. Most notably, ZIF8-SQ provides unparalleled aPDT action against methicillin-resistant Staphylococcus aureus (MRSA) and leads to complete loss of adherence of structurally robust bacterial biofilms. Finally, the nontoxic nature of the nanoconjugate toward human cells holds great promise for effective treatment of MRSA and other detrimental antibiotic-resistant microbes in clinical models.

Sensitizing of β-lactam resistance by tannic acid in methicillin-resistant S. aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections treatment of which is hard and failed, due to being resistant to all types of β-lactams, have been emerged in hospitals and community. Long-term usage of antibiotics and over doses of antibiotics used in the treatment of infections cause bacteria to develop resistance to antibiotics. β-lactams combined with tannic acid can be a good alternative to sensitize the resistance of β-lactams used in the treatment of MRSA, due to their synergistic activities. In this study, after minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) of sole tannic acid and β-lactam were investigated for each isolate, the synergistic activities of β-lactams combined with tannic acid against one MRSA ATCC 43300 and four MRSA clinical isolates were investigated with the concentrations starting at four fold of MICs of sole treatments of tannic acid and β-lactam by using checkerboard assay. To investigate sole and combination activities of tannic acid and β-lactams, MIC and MBCs were observed. Results of this study showed that the activities of β-lactams combined with tannic acid were synergistic and partially synergistic against MRSA isolates with FIC indexes ranged from 0.174 to 0.477 and 0.562 to 0.850, respectively. MIC of β-lactams were decreased 2-16 fold by sub-inhibitory concentrations of tannic acid without toxicity. Alternative treatment options of natural compounds such as tannic acid and β-lactams must be investigated further and developed to overcome the emergence of β-lactam resistance and treat MRSA infections by sensitizing the resistance of β-lactams.

Physiologically Based Pharmacokinetic Modeling for Trimethoprim and Sulfamethoxazole in Children.

The aims of this study were to (1) determine whether opportunistically collected data can be used to develop physiologically based pharmacokinetic (PBPK) models in pediatric patients; and (2) characterize age-related maturational changes in drug disposition for the renally eliminated and hepatically metabolized antibiotic trimethoprim (TMP)-sulfamethoxazole (SMX). We developed separate population PBPK models for TMP and SMX in children after oral administration of the combined TMP-SMX product and used sparse and opportunistically collected plasma concentration samples to validate our pediatric model. We evaluated predictability of the pediatric PBPK model based on the number of observed pediatric data out of the 90% prediction interval. We performed dosing simulations to target organ and tissue (skin) concentrations greater than the methicillin-resistant Staphylococcus aureus (MRSA) minimum inhibitory concentration (TMP 2mg/L; SMX 9.5mg/L) for at least 50% of the dosing interval. We found 67-87% and 71-91% of the observed data for TMP and SMX, respectively, were captured within the 90% prediction interval across five age groups, suggesting adequate fit of our model. Our model-rederived optimal dosing of TMP at the target tissue was in the range of recommended dosing for TMP-SMX in children in all age groups by current guidelines for the treatment of MRSA. We successfully developed a pediatric PBPK model of the combination antibiotic TMP-SMX using sparse and opportunistic pediatric pharmacokinetic samples. This novel and efficient approach has the potential to expand the use of PBPK modeling in pediatric drug development.

Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful modern pathogens. The same organism that lives as a commensal and is transmitted in both health-care and community settings is also a leading cause of bacteraemia, endocarditis, skin andsoft tissue infections, bone and joint infections and hospital-acquired infections. Genetically diverse, the epidemiology of MRSA is primarily characterized by the serial emergence of epidemic strains. Although its incidence has recently declined in some regions, MRSA still poses aformidable clinical threat, with persistently high morbidity and mortality. Successful treatment remains challenging and requires the evaluation of both novel antimicrobials and adjunctive aspects of care, such as infectious disease consultation, echocardiography and source control. Inthis Review, we provide an overview of basic and clinical MRSA research and summarize the expansive body of literature on the epidemiology, transmission, genetic diversity, evolution, surveillance and treatment of MRSA.

Anti-inflammatory effect of Garcinia mangostana Linn. pericarp extract in methicillin-resistant Staphylococcus aureus-induced superficial skin infection in mice

Garcinia mangostana (mangosteen) pericarp has antibacterial effects; however, information regarding its anti-inflammatory activity in vivo is limited. The anti-inflammatory effect of G. mangostana pericarp extract against methicillin-resistant Staphylococcus aureus (MRSA)-induced superficial skin infection was investigated in mice using a tape stripping model. G. mangostana pericarp ethanolic extract (GME) and its constituent, α-mangostin, were topically administered to mice with MRSA-induced superficial skin infection. MRSA-infected wounds treated with GME were completely healed on the 10th day of the study and the number of MRSA-colonies decreased from the first day of the study, whereas α-mangostin-treated wounds never completely healed with higher numbers of MRSA colonies. The epidermis of GME-treated wounds had nearly completely regenerated, with no inflammatory cell infiltration. In contrast, α-mangostin-treated wounds exhibited neutrophil infiltration and accumulation of mast cells. MRSA-infected wounds without treatment showed high expression of TNF-α, IL-6, IL-1β, and TLR-2 genes. In contrast, GME decreased mRNA levels, restoring expression of those genes to normal levels. Notably, α-mangostin did not down-regulate the expression of pro-inflammatory cytokines to the same extent as GME. Hence, GME is a promising alternative MRSA treatment because of its antibacterial, anti-inflammatory, and wound healing effects.

Association between single trough-based area under the curve estimation of vancomycin and treatment outcome among methicillin-resistant Staphylococcus aureus bacteremia patients.

Failure of antibiotic treatment increases mortality of critically ill patients. This study investigated the association between the treatment resolution of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and vancomycin pharmacokinetic variables. A total of 28 critically ill patients were included in this study. All data were collected from medical, microbiology and pharmacokinetic records. The clinical response was evaluated on the basis of clinical and microbiological parameters. The 24-h area under the curve (AUC<SUB>0-24</SUB>) was estimated from a single trough level using established equations. Out of the 28 patients, 46% were classified as responders to vancomycin treatment. The trough vancomycin concentration did not differ between the responders and non-responders (15.02 ± 6.16 and 14.83 ± 4.80 μg mL^-1; P = 0.929). High vancomycin minimum inhibitory concentration (MIC) was observed among the non-responders (P = 0.007). The ratio between vancomycin trough concentration and vancomycin MIC was significantly lower in the non-responder group (8.76 ± 3.43 vs. 12.29 ± 4.85 μg mL^-1; P = 0.034). The mean ratio of estimated AUC<SUB>0-24</SUB> and vancomycin MIC was 313.78 ± 117.17 μg h mL^-1 in the non-responder group and 464.44 ± 139.06 μg h mL^-1 in the responder group (P = 0.004). AUC<SUB>0-24</SUB>/MIC of ≥ 400 μg h mL^-1 was documented for 77% of the responders and 27% of the non-responders (c² = 7.03; P = 0.008). Ratio of trough concentration/MIC and AUC<SUB>0-24</SUB>/MIC of vancomycin are better predictors for MRSA treatment outcomes than trough vancomycin concentration or AUC<SUB>0-24</SUB> alone. The single trough-based estimated AUC may be sufficient for the monitoring of treatment response with vancomycin.

Risk Factors and Prevention of Surgical Site Infections Following Spinal Procedures.

Study Design:Focused literature review.Objective:The objective of this article was to help identify potential risk factors as well as strategies to help prevent surgical site infections (SSIs) in spine surgery.Methods:An article search was performed using PubMed, EMBASE, and the Cochrane database of systematic reviews using the terms “surgery” OR “surgical” AND “spine” OR “spinal” AND “infection”. Systematic review articles, meta-analyses, and clinical trials with more than 100 patients were reviewed.Results:Both patient and perioperative factors contribute to the development of SSIs. Patient factors such as smoking, obesity, diabetes, Methicillin-resistant Staphylococcus aureus (MRSA) colonization, and malnutrition are all modifiable risk factors that can lead to SSIs. Procedural steps, including preoperative MRSA screening and treatment for colonization, preoperative antibiotics, skin preparation, minimizing operative time, antibiotic or betadine irrigation, avoiding personnel turnover, and postoperative wound care have also been shown to decrease infection rates.Conclusion:There are several measures a spine practitioner may be able to take in the preoperative, intraoperative, and postoperative settings. Protocols to counsel patients regarding modification of preexisting risk factors and ensure adequate antimicrobial therapy in the perioperative period may be developed to reduce SSIs in spine surgery.

Take the initiative to reduce surgical site infections

Take the initiative to reduce surgical site infections

1223. Increasing Incidence of Methicillin-Resistant Staphylococcus aureus in Greenland

BackgroundThe first case of methicillin-resistant Staphylococcus aureus (MRSA) in Greenland was diagnosed in 2000 and led to the first guideline on screening and treatment for MRSA. Up to 2015 there were only 13 patients with MRSA but since then a nearly 4-fold increase in incidence has been seen. The objectives of this study were to analyze the reasons for this increase.MethodsMRSA data were collected from the laboratory surveillance database at Dronning Ingrids Hospital, typing results from the Reference Laboratory for Antimicrobial Resistance and Staphylococci at SSI, and the patient records.ResultsFrom 2000 to 2017, 48 patients (15 children and 33 adults) have been diagnosed with MRSA. Thirty patients were colonized with MRSA, predominantly in the nose and throat. Eighteen patients had infections: conjunctivitis, middle ear infections, wounds, skin abscesses, mastitis, surgical site infections, for example.The increase since 2015 was mainly due to three large outbreaks in three different cities: Aasiaat in 2014/2015 (seven persons with MRSA; three children and four adults), the capital Nuuk in 2016 (six persons with MRSA; two children and four adults) and Tasiilaq in 2017 (13 persons with MRSA; three children and ten adults). The first two outbreaks were community-acquired with transmission in families and the last one was community-acquired or community-onset hospital acquired. Each outbreak was caused by a specific MRSA-type: t902 CC22 in Aasiaat (unknown epidemiology), t3979 CC5 in Nuuk (probably from Australia), and t304 CC6 in Tasiilaq (probably from Denmark).MRSA was mainly imported from Denmark or abroad due to admission to hospital or due to traveling to high-endemic countries like Australia, but in some cases the epidemiology was unknown. Transmission occurred mainly in families with close contact.ConclusionThe increasing number of patients with MRSA in Greenland can be explained by factors such as import from Denmark or abroad due to admission to hospital or traveling, and transmission in Greenland. An ongoing surveillance, compliance to screening procedures (especially patients admitted to hospitals abroad) and guidelines for infection prevention and control are necessary in order to combat MRSA in Greenland in the future.Disclosures All authors: No reported disclosures.