Two cases of refractory methicillin-susceptible staphylococcus aureus endocarditis responsive to ertapenem

Persistent methicillin-sensitive staphylococcus aureus(MSSA)bacteremia is usually defined as persistent bacteremia despite 7 days of appropriate antibiotic therapy.While nafcillin,cefazolin,or oxacillin are excellent antimicrobial options,persistent MSSA is a commonly encountered phenomenon in clinical practice for which further guidelines on appropriate management are necessitated.Here we highlight two cases of MSSA bacteremia requiring salvage therapy with ertapenem.

Treatments and limitations for methicillin-resistant Staphylococcus aureus: A review of current literature

Methicillin-resistant Staphylococcus aureus(MRSA)has remained a major threat to healthcare;in both hospital and community settings over the past five decades.With the current use of antibiotics for a variety of infections,including MRSA,emerging resistance is a major concern.Currently available treatments have restrictions limiting their use.These issues include,but are not limited to,side effects,cross-resistance,lack of understanding of pharmacokinetics and clinical pharmacodynamics,gradual increment in minimal inhibitory concentration over the period(MIC creep)and ineffectiveness in dealing with bacterial biofilms.Despite availability of various therapeutic options for MRSA,the clinical cure rates remain low with high morbidity and mortality.Given these challenges with existing treatments,there is a need for development of novel agents for MRSA.Along with prompt infection control strategies and strict implementation of antibiotic stewardship,cautious use of newer anti-MRSA agents will be of utmost importance.This article reviews the treatments and limitations of MRSA management and highlights the future path.

Epidemiology,surveillance and control of methicillin-resistant Staphylococcus aureus:an Overview

Staphylococcus aureus(S.aureus) is one of the most common human pathogens,causing a wide range of afflictions from minor infections of the skin to serious wound infections,bacteraemia,pneumonia and endocarditis. Methicillin,the first semisynthetic derivative of penicillin,was a new hope to treat penicillin resistant 5.aureus in the early 1960s.Nevertheless,only one year after its introduction,the first methicillin-resistant 5.aureus (MRSA) strains were detected.There is no golden rule in the control of MRSA.Nevertheless,using surveillance cultures of patients and healthcare personnel,strictly enforced contact precautions,and judicious use of broad-spectrum antibiotics have helped several countries,including Finland,Denmark,and the Netherlands to keep MRSA at a very low level.Conversely,countries including China,Japan,US,Italy,Greece,UK, where stringent counter-measure were not able to be installed,MRSA have become hyper-endemic.Control of MRSA in those countries were obliged to concentrate available resources to prevent MRSA infections only at patients at high risk of serious morbidity and mortality.

Genotypic Characterization of Methicillin-resistant Staphylococcus aureus Isolated from Pigs and Retail Foods in China

Objective To investigate the genotypic diversity of Methicillin-resistant Staphylococcus aureus （MRSA） isolated from pigs and retail foods from different geographical areas in China and further to study the routes and rates of transmission of this pathogen from animals to food. Methods Seventy-one MRSA isolates were obtained from pigs and retail foods and then characterized by multi-locus sequencing typing （MLST）, spa typing, multiple-locus variable number of tandem repeat analysis （MLVA）, pulsed-field gel electrophoresis （PFGE）, and antimicrobial susceptibility testing. Results All isolated MRSA exhibited multi-drug resistance （MDR）. Greater diversity was found in food-associated MRSA （7 STs, 8 spa types, and 10 MLVA patterns） compared to pig-associated MRSA （3 STs, 1 spa type, and 6 MLVA patterns）. PFGE patterns were more diverse for pig-associated MRSA than those of food-associated isolates （40 vs. 11 pulse types）. Among the pig-associated isolates, CC9-ST9-t899-MC2236 was the most prevalent clone （96.4%）, and CC9-ST9-t437-MC621 （20.0%） was the predominant clone among the food-associated isolates. The CC9-ST9 isolates showed significantly higher antimicrobial resistance than other clones. Interestingly, CC398-ST398-t034 clone was identified from both pig- and food-associated isolates. Of note, some community- and hospital-associated MRSA strains （t030, t172, t1244, and t4549） were also identified as food-associated isolates. Conclusion CC9-ST9-t899-MC2236-MDR was the most predominant clone in pigs, but significant genetic diversity was observed in food-associated MRSA. Our results demonstrate the great need for improved surveillance of MRSA in livestock and food and effective prevention strategies to limit MDR-MRSA infections in China.

Detection and Characterization of Methicillin Resistant Staphylococcus aureus from Toilet and Classroom Door Handles in Selected Secondary Schools in Nairobi County

Background: Staphylococcus aureus is found on all surfaces especially in public areas like hospitals and schools and on frequently touched areas like toilet and classroom door handles. Methicillin resistant Staphylococcus aureus (MRSA) is a strain of Staphylococcus aureus which is resistant to methicillin. There are two types of MRSA: Community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) and hospital acquired methicillin resistant Staphylococcus aureus (HA-MRSA). MRSA in the community presents a significant reservoir that could enter into healthcare facilities and spread among patients and also a risk for immune compromised persons in the community. Methodology: The study aimed at determining the prevalence of MRSA isolated from toilet and classroom door handles as a potential source of infection to the students and the workers in selected schools in Nairobi, Kenya. The study also compared the prevalence of MRSA between boarding and non-boarding girls, boys and mixed (both girls and boys in the same school) secondary schools. Twelve secondary schools in Nairobi County were randomly selected and 306 samples from both the toilet and classroom door handles were collected using sterile swabs and transported to the laboratory. Isolation of Staphylococcus aureus was done by the use of selective media Mannitol salt agar, antibiotic susceptibility of isolates was done by disk diffusion method, and molecular detection of mecA and PVL genes were done by polymerase chain reaction (PCR). Results: The prevalence of S. aureus was 20% and 15% were MRSA positive by both Antimicrobial Susceptibility Test and PCR detection. 20% showed the presence of PVL genes, 8% showed the presence of both genes and 56% of isolates with mecA gene had PVL genes. Conclusion: The presence of MRSA in this study emphasizes the need to formulate hygiene measures to prevent possible spread of MRSA and other transmissible pathogens to students and workers in the schools.

Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus

Objective:To investigate the mechanism of antibacterial activity of luteoiin(LUT) against methicillin-resistant Staphylococcus aureus(MRSA).Methods:The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent ATPase inhibitors,and peptidoglycan(PGN) derived from Staphylococcus aureus(S.aureus).Also,transmission electron microscopy was used to monitor survival characteristics and changes in S.aureus morphology.Results:Compared to the LUT alone,the optical density of suspensions treated with the combination of 125 μg/mL Tris and 230 μg/mL DCCD were reduced to 60%and 46%,respectively.PGN(15.6 μg/mL) gradually impeded the activity of LUT,and PGN(62.5 μg/mL) completely blocked the activity of LUT on S.aureus.Conclusions:Increased susceptibility to LUT with me Tris and DCCD combinations is evident in all tested MRSA isolates.The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase.S.aureus PGN directly blocks the antibacterial activity of LUT,suggesting the direct binding of LUT with PGN.These findings may be validated for the development of antibacterial agent for low MRSA resistance.

Postoperation of preauricular fistula cellulitis caused by methicillin-resistant staphylococcus aureus infection

A one-year-old baby girl with one-month history of recurrent pus fluid exuding from her left preauricular sinus orifice, who failed multiple courses of surgical drainage of the abscess and persistent debridement for the wound, presented with MRSA infection. The patient was treated with linezolid for three days. Her pain and paresthesia resolved, and C-reactive protein decreased to normal.

Implantable cardioverter defibrillator lead-related methicillin resistant Staphylococcus aureus endocarditis:Importance of heightened awareness

Methicillin resistant Staphylococcus aureus(MRSA) septicemia is associated with high morbidity and mortality especially in patients with immunosuppression,diabetes,renal disease and endocarditis.There has been an increase in implantation of cardiac implantable electronic devices(CIED) with more cases of devicelead associated endocarditis been seen.A high index of suspicion is required to ensure patient outcomes are optimized.The excimer laser has been very efficient in helping to ensure successful lead extractions in patients with CIED infections.We present an unusual case report and literature review of MRSA septicemia from device-lead endocarditis and the importance of early recognition and prompt treatment.

Antimicrobial activity and synergism of Sami-Hyanglyun-Hwan with ciprofloxacin against methicillin-resistant Staphylococcus aureus

Objective: To investigate the antibacterial activity of SHHextracted with either water or ethanol against methicillin-resistant Staphylococcus aureus(MRSA) and combinatory antimicrobial effect with ciprofloxacin(CIP) by time kill assay and checkerboard dilution test. Methods: The antibacterial activity determined by broth dilution method indicated that the antibacterial activity of Sami-Hyanglyun-Hwan(SHH) water extract(SHHW) and SHH ethanol extract(SHHE) ranged from 250 to 2000 μg/m L and 125 to 1000 μg/m L against MRSA, respectively. Results: In the checkerboard method, the combinations of SHHE with CIP had a partial synergistic or synergistic effect against MRSA. The time-kill curves showed that a combined SHHE and CIP treatment reduced the bacterial counts dramatically after 24 h. Conclusions: The present study demonstrates the therapeutic ability of SHHE against MRSA infections.

A comparative evaluation of methicillin-resistant staphylococci isolated from harness racing-horses,breeding mares and riding-horses in Italy

Objective:To investigate the prevalence of methicillin-resistant staphylococci(MRS)which is a potencial risk factor of transmission between animals and humans in different types of horses(harness racing-horses,breeding mares and riding-horses)and to compare the antimicrobial resistance of the isolates.Methods:A total of 191 healthy horses,housed at different locations of the Campania Region(Italy),were included in the study.Nasal swab samples were collected from each nostril of the horses.The mecA gene was detected by a nested PCR technique.Antibiotic susceptibility was tested for each isolate.Results:MRS was isolated from nasal samples of 68/191(35.6%;95%CI:28.9%-42.9%)healthy horses.All isolates were coagulase-negative with the exception of two coagulase-positive MRS strains,identified as Staphylococcus aureus and Staphylococcus pseudintermedius.2/83(2.4%;95%,CI:0.4%-9.2%).Interestingly,both coagulase-positive MRS isolates were from harness racing-horses.These horses also presented a significantly higher positivity for MRS(53.3%;95%CI:40.1%-66.1%)than the breeding mares and riding-horses groups.Antibiotic susceptibility testing showed difference between isolates due to different origins except for an almost common high resistance to aminopenicillins,such as ampicillin and amoxicillin.Conclusions:It can be concluded that harness racing-horses may act as a significant reservoir of MRS as compared to breeding mares and riding-horses.

Severe bacteremia community-acquired methicillinresistant Staphylococcus aureus pneumonia in a young adult

Dear editor,Adults with community-acquired methicillin-resistant Staphylococcus aureus(CA-MRSA)are prone to necrotizing pneumonia,bacteremia,and high mortality.Several studies have reported the disease worldwide,but only a few cases of CA-MRSA pneumonia in children and adolescents have been reported in China.[1]No CA-MRSA was detected in the pathogens of community-acquired respiratory tract infections in Chinese adults from 2009 to 2010.During the influenza epidemic,such as COVID-19,viral infections are followed by repeated bacterial infections,and methicillin-sensitive Staphylococcus aureus(MSSA)and MRSA pneumonia are known complications.[2]Thus,identifying and treating these infections is a tricky clinical issue.A case of CA-MRSA pneumonia with bloodstream infection and pneumothorax was successfully treated in our hospital in January 2018.Herein,we presented a case report based on previous studies.

Bacteriophage Biocontrol Rescues Mice Bacteremic of Clinically Isolated Mastitis from Dairy Cows Associated with Methicillin-Resistant <i>Staphyloccocus aureus</i>

Methicillin-resistant Staphylococcus aureus (MRSA) is among the most alarming pathogens affecting both humans and the global bovine industry. The current control measures in hospitals and on farms for MRSA have proven to be inadequate leaving a need for new rapid control methods to curb MRSA infections in situ. New control measures for bacterial infection are widely sought, with particular interest in the applications for bacteriophages (phages) as a biocontrol or therapeutic agent. The current study uses a wild highly lytic phage isolated from cow’s milk taken from three farms in Baghdad, Iraq. The resulting phage was able to rescue 100% of the mice from a median lethal dose (LD50) or (1 × 108 CFU mL-1 per mouse) for MRSA wild isolates achieved when the phage: bacteria ratio was 100:1. Even when treatment was delayed for 6 h post lethal infection, to the point where all mice were moribund, 80% of them were rescued by a single injection of this phage preparation. Based on the current results, a comprehensive study is needed to guide further research on the MRSA phage as a biocontrol for MRSA mastitis in dairy cows to replace or reduce the use of antibiotics in animal husbandry.

Prevalence and Antimicrobial Susceptibility Pattern of Methicillin Resistance Staphylococcus in a Sudanese Surgical Ward

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is important nosocomial pathogen. Aim: In this paper, we determined the prevalence and the antibiotic susceptibility pattern of (MRSA) in a Sudanese surgical ward. Method: A total of 200 post-operative surgical specimens were collected from patients hospitalized in gastrointestinal tract (GIT) surgical ward in Ibn Sina hospital, Khartoum, Sudan and were subjected to MRSA screening and sensitivity test. Key findings: Out of 35 strains of Staphylococcus aureus isolated from surgical samples, 25 (71.4%) were found to be MRSA. Almost all MRSA strains were resistance to Methicillin, 96% to Ofloxacin, 92% to Pencillin G, 24% to Amikacin and 4% to Vancomycin. Cross-resistance was obviously detected. Conclusion: The present study detected alarming levels of S. aureus (MRSA) isolates, at the same time presence of high cross-resistance to other antibiotics.

Synergistic Effect between Fucoidan and Antibiotics against Clinic Methicillin-Resistant <i>Staphylococcus aureus</i>

Fucoidan is a sulfated polysaccharide that is primarily extracted from brown seaweeds which has been broadly studied in recent years due to its numerous biological properties, including anticoagulant, antithrombotic, antitumor, and antiviral activities. In this study, fucoidan was evaluated against clinic isolated methicillin-resistant Staphylococcus aureus (MRSA) 1 - 20, either alone or with antibiotics, via broth dilution method and checkerboard and time kill assay. Minimum inhibitory concentrations (MICs)/Minimum bactericidal concentrations (MBCs) values for the fucoidan against all the tested bacteria ranged between 64 - 512/256 - 2048 microg/mL, for ampicillin 32 - 1024/64 - 1024 microg/mL and for oxacillin 8 - 64/16 - 256 microg/mL respectively. Furthermore, the MIC and MBC were reduced to one half-eighth as a result of the combination of the fucoidan with antibiotics. 2 - 6 hours of treatment with 1/2 MIC of fucoidan with 1/2 MIC of antibiotics resulted from an increase of the rate of killing in units of CFU/mL to a greater degree than was observed with alone. These results suggest that fucoidan could be employed as a natural antibacterial agent against multi-drug bacteria.

Combination of Acacetin with Antibiotics against Methicillin Resistant <i>Staphylococcus aureus</i>Isolated from Clinical Specimens

Methicillin-restitant Staphylococcus aureus (MRSA) is very dangerous bacteria and one of the most feared nosocomial germs. In this study, acacetin was evaluated against 20 clinical isolates of MRSA, either alone or in combination with antibiotics. The acacetin exhibited a good activity against isolates MRSA with MICs/MBCs ranged between 10-80/20-160 μg/mL, for ampicillin 64-1024/128-2048 μg/mL, and for oxacillin 8-32/16-64 μg/mL. The combination of acacetin plus oxacillin or ampicillin was reduced by ≥4-fold against isolates MRSA tested, evidencing a synergistic effect as defined by a FICI of ≤0.5. Furthermore, a time-kill study evaluating the growth of the tested bacteria was completely attenuated after 2-5 h of treatment with the 1/2 MIC of acacetin, regardless of whether it was administered alone or with oxacillin (1/2 MIC) or ampicillin (1/2 MIC). In conclusion, acacetin exerted synergistic effects when administered with oxacillin or ampicillin and the antibacterial activity and resistant regulation of acacetin against clinical isolates of MRSA might be useful in controlling MRSA infections.

The prevalence of methicillin-resistant Staphylococcus aureus colonization in emergency department fast track patients

BACKGROUND:Over the past two decades,methicillin-resistant Staphylococcus aureus(MRSA) has evolved from a hospital-associated infection to a significant public health threat in the community,causing outbreaks of soft tissue infections in otherwise healthy individuals.The goal of this study was to determine the prevalence of nasal MRSA colonization in low acuity Emergency Department(ED) Fast Track patients in order to better characterize the epidemiology of this pathogen.METHODS:We conducted a cross-sectional study of a convenience sample of adult patients from our ED Fast Track.Nasal swabs were analyzed for MRSA using a polymerase chain reaction assay.Study participants completed a survey assessing traditional risk factors for CA-MRSA colonization.RESULTS:A total of 106 ED Fast Track patients were tested.Four(3.8%,95%CI 1.5%-9.3%)were MRSA positive.Three traditional CA-MRSA risk factors(personal history of abscess,family history of abscess,and participation in contact sports) were examined.In patients with a positive MRSA nasal swab,only a personal prior history of abscess retained significance(OR 33,95%C11.7-676,P=0.02).CONCLUSION:This study found a higher prevalence of nasal MRSA colonization in low acuity ED Fast Track patients compared with historical community surveillance studies.A personal history of prior abscess was a significant risk for CA-MRSA carriage.

Treatment of methicillin-resistant Staphylococcus aureus infections:Importance of high vancomycin minumum inhibitory concentrations

Staphylococcus aureus(SA) infections remain a major cause of morbidity and mortality despite the availability of numerous effective anti-staphylococcal antibiotics.This organism is responsible for both nosocomial and community-acquired infections ranging from relatively minor skin and soft tissue infections to life-threateningsystemic infections.The increasing incidence of methicillin-resistant strains has granted an increasing use of vancomycin causing a covert progressive increase of its minimum inhibitory concentration(MIC)(dubbed the MIC "creep").In this way,the emergence of vancomycinintermediate SA(VISA) strains and heteroresistantVISA has raised concern for the scarcity of alternative treatment options.Equally alarming,though fortunately less frequent,is the emergence of vancomycin-resistant SA.These strains show different mechanisms of resistance but have similar problems in terms of therapeutic approach.Ultimately,various debate issues have arisen regarding the emergence of SA strains with a minimum inhibitory concentration sitting on the superior limit of the sensitivity range(i.e.,MIC = 2 μg/mL).These strains have shown certain resilience to vancomycin and a different clinical behaviour regardless of vancomycin use,both in methicillin-resistant SA and in methicillin-sensitive SA.The aim of this text is to revise the clinical impact and consequences of the emergence of reduced vancomycin susceptibility SA strains,and the different optimal treatment options known.

Intestinal carriage of methicillin resistant Staphylococcus aureus and extended-spectrum β-Lactamase-producing Enterobacteriacae in hospitalized and nonhospitalized patients and their clinical implications

Objective:To determine the clinical implication of and intestinal carriage with methicillin resistant Staphylococcus aureus(MRSA) and extended spectrumβ-lactamase(ESBL)-producing Enterobacteriacae.Methods: A total of 180 stool specimens were screened for MRSA and ESBL-producing enterobacteria.Identification of ESBL- producing Enterobacteriacae was done by MicroScan Walk Away 96 system(Dade Behring Inc.,West Sacramento,CA 95691,USA ) and confirmation by double-disc synergy test.MRSA was identified by disc diffusion using 30μg cefoxitin disc and the MicroScan.Results:The rate of fecal MRSA carriage was 7.8% (14/180),35.7%(5 /14) were recovered from surgical wards.Three patients(21,4%) had MRSA recovered from other body sites,and 2(14.2%) had in addition ESBL -producing Escherichia coli(E.coli) and Klebsiella pneumoniae(K.pneumoniae) respectively.Four(28.5%) patients with MRSA fical carriage died. MRSA fecal carriage was recovered from both inpatients and outpatients.Four(2.2%) cases carried ESBL-producing Enterobacteriacae in feces.Three(75%) were from intensive care unit(ICU).One patient had both ESBL-producing E.coli and K.pneumoniae from stool as well as E.coli from tracheal aspirate.Two ICU patients with fecal ESBL died.Conclusion:Fecal screening for MRSA and ESBL of all patients at high risk admitted to different hospital wards and ICUs and implementing infection control measures were recommended.

Identification of Panton-Valentine leukocidin virulence gene in methicillin-resistant Staphylococcus aureus isolated from clinical specimens of burn patients in Zare Hospitals of Sari, Iran

Objective:To identify the pathogenic gene of Panton-Valentine leukocidin in methicillin-resistant Staphylococcus aureus strain isolated from clinical specimens of burn patients in Shaheed Zare Burn Hospital.Methods:A total of 104 samples of Staphylococcus were collected and 78 aureus samples were isolated from Zare Hospital patients from November 2016 to July 2017.All isolates were identified using a standard biochemical and laboratory methodology in accordance with CLSI principles,and disk agar diffusion antibiogram were performed to identify methicillin resistant colonies.Then the presence of the Panton-Valentine leukocidin gene was tested by PCR.Results:Of the methicillin-resistant Staphylococcus aureus samples,80%were negative for the Panton-Valentine leukocidin gene,and only 20%of the samples had Panton-Valentine leukocidin gene.Male and female patients showed no significant difference in the positivity rate of Panton-Valentine leukocidin gene(16.12%vs.33.33%)(P=0.25).Besides,there was no significant difference in bacterial resistance or susceptibility to antibiotics between samples with or without the Panton-Valentine leukocidin gene.Conclusions:In recent years,increased resistance has been a serious threat.The resistance or susceptibility of Staphylococcus aureus strains to different antibiotics is different in different geographical locations.

Co-Habitation of <i>Staphylococcus lugdunensis</i>with <i>Staphylococcus aureus</i>Resistant to Methicillin and Vancomycin in the Nasal Snares of Laboratory Rats

The public health problem created by multidrug resistant bacteria in the 21st century continues to receive attention by researchers all over the world. As the production of new antibiotics is not commeasurable with the rate of evolvement of MDR bacteria, the news of a proposed new antibiotic “Lugdunin” is much awaited and a welcomed development. Lugdunin is produced by Staphylococcus lugdunensis and has the ability to kill S. aureus. Both bacteria are nasal colonizers. The present investigation looks into the antibiotic susceptibility pattern of co-habitation of S. lugdunensis with methicillin and vancomycin resistant Staphylococcus aureus in laboratory bred Wister rats. Nasal swabs of anaesthetized rats were collected using a sterile cotton swab moistened in 0.9% saline solution. All swabs were inoculated into nutrient broth, cultured at 37°C for 24 hrs. Overnight bacterial growth plated on blood agar and incubated at 37°C for 24 hrs. Organism identification and antibiotic susceptibility test were by using BioMerieux VITEK 2 compact automated system (BioMerieux, Marcy I’Etoile France), according to the manufacturers guidelines. Results obtained showed co-habitation of S. aureus with co-agulase negative bacteria, inclusive of S. lugdunensis. All the isolates were resistant to methicillin with a 33.3% resistance to vancomycin. The difference between the number of antibiotic resistant or sensitive varied statistically among the Staphylococcal isolates. For S. aureus 1, the difference was significant with p-value 0.034 but not significant for isolates 2, 3 and 4 with p-values of 0.158, 0.477 and 0.158 respectively. A statistically significant difference was seen with S. lugdunensis. The result from the study therefore, showed that the colonization of the nasal snares of the laboratory bred rats with S. aureus and other co-agulase negative Staphylococci was not affected by the presence of S. lugdunensis.