Vancomycin-resistant Methicillin-resistant Staphylococcus Aureus Research Articles

Application of InP/ZnSe/ZnS Quantum Dots in the Treatment of Experimental Antibiotic-Resistant Endophthalmitis <i>in vivo</i>

Purpose: modeling of experimental antibiotic-resistant endophthalmitis on laboratory animals model describing the interaction of quantum dots and a biological organism and its physicochemical and kinetic aspects.Material and methods. The object of the study is laboratory New Zealand rabbits (2 male, age 4 months, weight 3.5 kg). The inflammation inductor is the culture of Methicillin-Resistant Staphylococcus Aureus (MRSA). 1 mg/0.05 ml of vancomycin in combination with 0.5 μg (0.01 %)/0.05 ml by a solution of quantum dots InP/ZnSe/ZnS 660 was intravitreally administrated to the first rabbit. 1 mg/0.1 ml of vancomycin was intravitreally administrated to the second rabbit. Dynamic observation of the clinical process was performed daily by photo registration of the front segment and ultrasonic sonography.Results. The conjugate based on 1 mg/0.05 ml vancomycin coupled with 0.5 μg (0.01 %)/0.05 ml quantum dots InP/ZnSe/ZnS 660 demonstrated high anti-infectious activity against vancomycin-resistant MRSA. It was shown that the effect of the above solution on MRSA is described by the one-time ability of quantum dots by using electron microscopy. The presence of superoxide radicals O2–• generation in an aqueous solution of quantum dots under the action of blue light has also been proven by spectrophotometric method.Conclusion. Conjugates based on quantum dots can be considered as one of the promising directions of treatment of antibiotic-resistant endophthalmitis.

Overview Methicillin-Resistant Staphylococcus Aureus Combination Treatment Options in Vivo and in Vitro

The spread of multidrug-resistant Staphylococcus aureus continues to threaten global health. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the common causes of bacterial infections in hospitals and communities. Despite vancomycin being an effective treatment for MRSA, from 2006 to 2020, vancomycin-resistant MRSA increased 3.5-fold, from 5% to 7%. Bacterial genome mutations, as well as bacteria’s ability to transfer genetic material with other bacteria, allowing them to obtain resistance genes from different strains, are all factors contributing to the development of vancomycin resistance in MRSA. As a result, combination therapy may be a potential treatment for MRSA infection. We searched in PubMed and Google Scholar, and our search yielded 92 articles, out of which 74 full-text articles were reviewed and 56 were selected for this study. This literature review examines combination therapies for MRSA infections, such as -Lactams with vancomycin, linezolid and imipenem, daptomycin and ceftaroline. The review yielded several studies looking at the synergy between -lactams and vancomycin. Although linezolid and rifampicin demonstrate synergy against MRSA in vivo and in vitro in various invasion diseases, more clinical research is required to prove their efficacy. Furthermore, daptomycin plus ceftaroline shows synergy for refractory staphylococcal bacteremia in vivo and in vitro. Combining ceftaroline and daptomycin has two benefits: they work synergistically together and make the innate host defense peptide cathelicidin leucine-leucine-37 (LL-37) more sensitizing. Ceftaroline plus daptomycin was recently used in MRSA biofilm infections, demonstrating a potentially promising treatment as the first combination used without side effects in humans. Keywords: Bacteremia, Vancomycin, Daptomycin, Ceftaroline, Staphylococcus aureus, MRSA.

Future Trends in the Treatment of MRSA in Pakistan


 Background: The Methicillin resistant Staphylococcus aureus (MRSA) is accountable for community and hospital acquired infections. Due to over and misuse of antibiotics, MRSA isolates are becoming multidrug resistant even with linezolid and vancomycin. The objective of this study was to determine recent antimicrobial profile of MRSA, isolated from different clinical samples and current treatment options for MRSA, other than vancomycin and Linezolid.
 Methodology: This cross-sectional study was conducted at Foundation university medical college from Jan 2019 to Dec 2020. Total 918 samples of blood, pus swab, throat swab, tracheal swab, wound swab, endotracheal tube (ETT) tips, Catheter tips, axillary swab and suction tips received by using aseptic techniques, for culture and sensitivity in different hospitals of Rawalpindi and Islamabad, were taken. Isolated pathogens were identified using standard protocols and susceptibility testing was done by Kirby-Bauer disc diffusion method.
 Results: Out of 918 samples, MRSA was isolated in 96 (10.4%) samples and most frequently observed in 27% (n=26) blood samples. The mean age of enrolled patients was 52.02 (SD±16.1) years, the infection was largely seen in age group 46-55(24%) and in 57% (n=52) male population. MRSA showed higher resistance to levofloxacin 78.1% (n=75), ciprofloxacin 75% (n=72), erythromycin 70.8% (n=68) and gentamycin 62.5% (n=60). The susceptibility of older drug chloramphenicol and Trimethoprim-sulfamethoxazole was found 61% & 49% respectively. MRSA isolates were highly susceptible to vancomycin (96.8%), linezolid (89.5%) and teicoplanin (70.85%). Alarmingly, 2.1% (n=2) MRSA isolates showed resistance to vancomycin.
 Conclusion:Vancomycin resistant MRSA is a matter of great concern, because of unawareness among health administrative departments and public, self-medication, lack of surveillance system and non-availability of antibiotic policy. 
 Keywords: Antibiotics, MRSA, Vancomycin, Chloramphenicol

Co-occurrence of antibiotic resistance and virulence Genes in Methicillin Resistant Staphylococcus aureus (MRSA) Isolates from Pakistan.

Methicillin resistant Staphylococcus aureus (MRSA) is one of the major human pathogen that is associated with hospital as well as community acquired infections and is responsible for huge amount of life-threatening diseases. Objective of the study was to determine MRSA prevalence, their antibiotic sensitivity patterns, frequency of virulence genes (sea, seb, sed, tst, hla, hld) and their co-occurrence with resistance marker mecA among Rawalpindi and its nearby regions of Pakistani clinical isolates. The present study was carried out to identify the virulence and antibiotic resistance genes that co-occur in MRSA through polymerase chain reaction. Antibiotic sensitivity, presence of virulence genes and their co-occurrence with resistance marker mecA were analyzed. These isolates were found resistant to number of antibiotics i.e. Amoxicillin (16.1%), Cefixime (48.38%), Doxycycline (27.415), Trimethoprim/sulfamethoxazole (37.09%), Clindamycin (30.64%), Erythromycin (83.87%), Penicillin (100%), Vancomycin (4.83%), Ciprofloxacin (70.96%), Tetracycline (20%), Linezolid (3.22%) and Fusidic acid (11.295). The frequency of antibiotic resistant gene (mecA) was 69.35% and that of virulence genes hla, hld, sea, seb, sed and tst was 100, 100, 53.2, 30.6, 3.2 and 24.2% respectively. Amongst all examined genes, hla and hld genes had the highest and sed gene had the lowest frequency. The maximum coexistence of genes was observed for hla+hld+mecA gene combination (42 out of 62 isolates). This study reports the presence of multidrug resistant, vancomycin-resistant and mecA negative MRSA isolates in infected patients of Rawalpindi and nearby regions of Pakistan that may have attributed to treatment failures, adaptability of new virulence characteristics and spread of antibiotic resistance.

Methicillin-Resistant <i>Staphylococcus aureus</i> May Also Be Resistant to Clindamycin and Vancomycin

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a global superbug widely distributed in hospitals, communities and livestock settings. This study investigated the presence and molecular characterization of MRSA co-resistance to clindamycin and vancomycin in the southeastern region of Nigeria. The susceptibility of these organisms to other selected antibiotics was also investigated. Method: Biological samples were obtained from consenting patients from three establishments in Enugu, Nigeria and cultured for isolation and purification. The pure isolates were subjected to antimicrobial susceptibility profiling using conventional antibiotics. The genomic DNAs of the pure isolates were isolated using the Promega genomic DNA purification kit while the antibiotic resistance genes (mecA) genes were identified using a multiplex polymerase chain reaction. Also, the minimum inhibitory concentration of the clindamycin and vancomycin antibiotics was determined as well as their combined activity on the MRSA isolates. Results: A large proportion (71%) of the MRSA isolates was from urine samples and then from the High Vaginal Swab (19%). All the isolates were resistant to cloxacillin while 95% were resistant to ciprofloxacin. MRSA isolates demonstrated resistance to clindamycin (with MIC of 23.44 - 250 μg/ml) and to vancomycin (with MIC of 62.5 - 250 μg/ml). The isolated MRSA also demonstrated multidrug-resistant traits. The combined effects of vancomycin and clindamycin against different species of MRSA exhibited additive, antagonistic and indifferent effects and none had a synergistic effect. Multiplex Polymerase Chain Reaction revealed that the majority of the strains were positive for the 162-bp internal fragment of the mecA gene of MRSA and basically displayed SCCmec type III, indicating that they were multidrug-resistant and hospital-acquired. Conclusion: Clindamycin and vancomycin-resistant MRSA infections are also within the Eastern region of Nigeria as found in other countries of the world. This superbug, therefore, may require drastic and urgent measures to curtail its spread and attendant healthcare challenges like outbreaks of infections. In addition, strict adherence to antibiotic policy and continuous surveillance is highly advocated.

Fight Against Antimicrobial Resistance: We Always Need New Antibacterials but for Right Bacteria.

Antimicrobial resistance in bacteria is frightening, especially resistance in Gram-negative Bacteria (GNB). In 2017, the World Health Organization (WHO) published a list of 12 bacteria that represent a threat to human health, and among these, a majority of GNB. Antibiotic resistance is a complex and relatively old phenomenon that is the consequence of several factors. The first factor is the vertiginous drop in research and development of new antibacterials. In fact, many companies simply stop this R&D activity. The finding is simple: there are enough antibiotics to treat the different types of infection that clinicians face. The second factor is the appearance and spread of resistant or even multidrug-resistant bacteria. For a long time, this situation remained rather confidential, almost anecdotal. It was not until the end of the 1980s that awareness emerged. It was the time of Vancomycin-Resistance Enterococci (VRE), and the threat of Vancomycin-Resistant MRSA (Methicillin-Resistant Staphylococcus aureus). After this, there has been renewed interest but only in anti-Gram positive antibacterials. Today, the threat is GNB, and we have no new molecules with innovative mechanism of action to fight effectively against these bugs. However, the war against antimicrobial resistance is not lost. We must continue the fight, which requires a better knowledge of the mechanisms of action of anti-infectious agents and concomitantly the mechanisms of resistance of infectious agents.

Monitoring of multiresistant community-associated MRSA strains from patients with pathological processes of different localization

The therapy of infections, caused by methicillin-resistant Staphylococcus aureus (MRSA) with multiple resistance to antibiotics remains one of the most acute problems all over the world. It is all the more complicated since a priori the MSRA strains are not sensitive to the group of β-lactam antibiotics and multiresistant isolates are resistant to other groups of antimicrobial preparations, including antibiotics of choice (rifampicin, vancomycin, fusidic acid, co-trimoxazole and linezolid). From the samples of biomaterials of patients with pathological processes of different localization, we isolated 335 strains of bacteria, which were identified as Staphylococcus aureus, 169 (50.4%) of which were methicillin-resistant variants: 57.5% cultures were isolated from the nasal discharge; 50.7% – from faeces at intestinal dysbioses; by 40.0% – from conjunctival discharge, pharyngeal swab, outer ear swab and sputum; 33.3% – from urine samples. Antibiotic susceptibility of the isolated cultures was estimated by the disc-diffusion method and the method of serial dilution. The MRSA strains appeared to be most resistant to gentamycin, erythromycin (by 59.5% of cultures) and ciprofloxacin (53.3% of isolates), most sensitive – to vancomycin, co-trimoxazole and fusidic acid. The frequency of isolation of the cultures that are resistant to antibiotics did not exceed 4.1%. Rifampicin suppressed the growth of 75.8% and linezolid – of 100.0% of strains. Depending on the kind of biomaterial taken, MRSA strains, isolated from the nasal cavity, outer ear, urine samples, samples of sputum and faeces at intestinal dysbioses proved to be most resistant to the tested antimicrobial preparations. Rifampicin- and vancomycin-resistant strains of methicillin-resistant staphylococci made up 21.3% of the total number of the detected MRSA. They were most often isolated from the clinical samples taken from the nasal cavity and faeces. When determining minimal inhibitory concentration (MIC) of rifampicin and vancomycin, which are antibiotics of choice for treatment of infections caused by multiresistant MRSA, it was found that for 55.5% of the MRSA strains isolated from faeces, MIC of rifampicin coincided with the threshold value for this antibiotic and for 44.5%, it exceeded the threshold value by 2 times (4 µg/ml). 22.2% of them were characterized by the critical value of susceptibility to vancomycin (MIC ≥ 2 µg/ml). From rifampicin- and vancomycin-resistant MRSA stains, isolated from the nasal cavity, MIC of rifampicin coincided with the threshold value for this antibiotic for 66.7% of cultures, and exceeded it at least by 2 times for 33.3%. 11.1% of them were characterized by the critical level of susceptibility to vancomycin (MIC ≥ 2 µg/ml) and by 3.7% of strains exceeded MIC by 2 and 4 times respectively (4 and 8 µg/ml).

The emergence of vancomycin-resistant Staphylococcus aureus in an intensive care unit in Kerman, Iran.

Methicillin-resistant Staphylococcus aureus (MRSA) is aglobal threat to public health. This study is the first report of the emergence of vancomycin-resistant MRSA in Kerman, Iran. During a period of 15months, atotal of 205clinical isolates of S.aureus were collected from three university hospitals affiliated with the Kerman University of Medical Science, Kerman, Iran. Screening of methicillin and vancomycin resistance was carried out by phenotypic methods. The resistance and virulence genes of vancomycin-resistant isolates were detected by polymerase chain reaction (PCR). Staphylococcal cassette chromosome mec (SCCmec) and spa typing were used for molecular typing of vancomycin-resistant isolates. Two S.aureus isolates were considered vancomycin-resistant by phenotypic and genotypic methods. Both isolates showed a minimum inhibitory concentration (MIC)≥ 64 µg/ml and belonged to SCCmecIII and spa type t030. Finding vancomycin-resistant S.aureus (VRSA) isolates represents aserious problem. More stringent infection control policies are recommended to prevent transmission of such life-threatening isolates in the hospital setting.

Daptomycin resistance in methicillin-resistant Staphylococcus aureus: a report from Southern India.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection of the wound may cause MRSA bacteremia with increased mortality, making it important to treat the infection. The increasing prevalence of MRSA accentuates the need for an effective therapy.1 Daptomycin is a cyclic lipopeptide antibiotic derived from Streptomyces roseosporus, which shows a potent bactericidal activity against most Gram-positive organisms including MRSA.1,2 Daptomycin received FDA approval in 2003 and was launched overseas. However it was approved for use in India after over 4 years (in 2008) without conducting any clinical trial in Indian population.3 Prior to this, a Sentry Antimicrobial Surveillance Program (2006-2007) performed in 14 medical centers in 13 Indian cities observed 100% susceptibility of the MRSA strains to Daptomycin.1 Following its introduction, limited data is available on the level of resistance to daptomycin in MRSA strains in India, making it important to have knowledge of the contemporary susceptibility levels. The present study was conducted in St. John's Medical College Hospital, a tertiary care multi-specialty hospital in Bangalore, India catering to patients of all socio-economic classes. We retrospectively determined the minimum inhibitory concentration (MIC) of daptomycin for clinically relevant, non-repetitive 30 MRSA and 20 methicillin-sensitive Staphylococcus aureus (MSSA) isolates randomly selected from 1615 Staphylococcus aureus isolates obtained from pus and wound swab samples (n=6687) submitted to the microbiology laboratory for aerobic culture and sensitivity profiling during January 2011 to December 2011. Among the 30 strains of MRSA, 22 strains were from hospital-acquired (HA)-MRSA infection and 8 strains were from community-acquired (CA)-MRSA infection. The majority of the patients harboring these MRSA strains were male (70%) and belonged to the age groups 21-40 years (46.7%), followed by 41-60 years (26.7%), ≤20 years (16.7%) and 61-80 years (10%). The patients harboring the studied MSSA strains were predominantly females (60%) and belonging to the age groups 21-40 years (45%), followed by 41-60 years (25%), 61-80 years and ≤20 years (15% each). The antibiotic resistance patterns of these isolates were determined by Kirby-Bauer disc diffusion method as per CLSI guidelines. The MIC for daptomycin (range: 0.016-256 μg/mL) was performed by E-test (bioMerieux, SA, France) according to CLSI guidelines. ATCC 29213 Staphylococcus aureus strain was used as a control. Table 1 shows the antibiotic resistance pattern of the strains included in this study. Vancomycin resistance by disc diffusion method was observed in 7% of the MRSA (n=2) and 5% (n=1) of the MSSA strains. All the isolates were susceptible to teicoplanin. The MIC levels of daptomycin against the MRSA and MSSA clinical isolates studied are shown in the Table 2. The MIC value for S. aureus ATCC 29213 was within the range 0.38-0.5 μg/mL. Daptomycin resistance in MRSA strains was observed at a low level of 6.7% (2/30). All the MRSA strains showed a MIC50/MIC90 of 0.38/1 μg/mL against daptomycin (MIC range: 0.19-2 μg/mL). Two HA-MRSA strains showed resistance to daptomycin (MIC: 2 μg/mL), retaining susceptibility to vancomycin. Daptomycin showed potent activity (MIC: ≤0.38 μg/mL) against vancomycin resistant MRSA (n=2) isolates. However since the MIC was not performed for vancomycin we could not ascertain whether these two strains were vancomycin resistant Staphylococcus aureus (VRSA) or vancomycin intermediate Staphylococcus aureus (VISA). It was further observed that the CA-MRSA strains (MIC50/MIC90: 0.25/0.5 μg/mL) were inhibited at two-fold lower MIC than HA-MRSA strains (MIC50/MIC90: 0.5/1 μg/mL). None of the twenty MSSA strains showed resistance to daptomycin (MIC50/MIC90: 0.38/1; range: 0.19-1 μg/mL). Table 1. Antibiotic resistance pattern of the MRSA and MSSA clinical isolates Table 2. Daptomycin minimum inhibitory concentration levels in MRSA and MSSA clinical isolates Although the sample size was small, daptomycin showed a good potency, inhibiting 93% of the MRSA strains. Our data supports the previous studies, showing good activity of daptomycin against MRSA strains. Earlier studies from India have reported daptomycin resistance in MRSA strains ranging from 0% to 10%.1,4–8 The studies reporting daptomycin resistance in Indian MRSA strains were from northern India (10%) and western India (6.25%).7, 8 To our knowledge for the first time we are reporting daptomycin resistance in MRSA (6.7%) from Southern India. With a well-documented safety profile and increased success rate in MRSA infection, daptomycin can be a viable therapeutic option for patients with MRSA wound infection. However in view of daptomycin resistant strains observed in our study we suggest that daptomycin MIC should be monitored to prevent treatment failure from possible emergence of strains with reduced susceptibility.

Antistaphylococcal activity of oritavancin and its synergistic effect in combination with other antimicrobial agents.

Oritavancin exhibited in vitro activity against 169 strains of vancomycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) with MICs ranging from 0.03 to 1 μg/ml and against vancomycin-intermediate MRSA (VISA; n = 29), heterogeneous vancomycin-intermediate MRSA (hVISA; n = 5), and vancomycin-resistant MRSA (n = 5) strains, with MICs ranging from 0.12 to 4 μg/ml. For 10 MRSA isolates comprising 5 VISA and 5 hVISA strains, synergy between oritavancin and gentamicin, linezolid, or rifampin was observed against most of the strains tested using a time-kill method.

Hand Hygiene Promotion in a Hospital Setting through the WHO Multimodal Hand Hygiene Improvement Strategy

Background: This study evaluated the frequency and types of hand hygiene practices among healthcare workers directed by the WHO multimodal hand hygiene improvement strategy, and investigated the effect of hand hygiene practice on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) isolation and MRSA acquisition rate and colonization pressure. Methods: A quasi-experimental study was performed at a tertiary care university hospital with 850 beds from January to September 2012. We assessed the hospital hand hygiene program using the WHO hand hygiene self-assessment framework. The WHO multimodal strategy was used for healthcare workers with low indexes, and the subjects were reassessed. Results: Hand hygiene compliance increased significantly from a pre-intervention rate of 58.7% to 72.6% post-intervention. MRSA and VRE isolation rates decreased from 1.69 per 1000 patient days to 1.41 and from 0.17 to 0.11, respectively. In intensive care units (ICUs), hand hygiene compliance rate rose to 77.9%, with a total score of 4.16 points out of 5 being awarded for the hand hygiene method, which was higher than that for the other care units. The pre-intervention MRSA acquisition rate in the ICU decreased from 7.47% to 4.30% post-intervention. This was associated with a decrease in the MRSA colonization pressure over the intervention period (26.2% to 16.9%). Conclusion: The utilization of the WHO multimodal strategy for improvement of hand hygiene increased the hand hygiene compliance rate and was effective in predicting a decreased rate of cross-infection, MRSA acquisition, and colonization pressure. We conclude that the implementation of such improvement strategies is crucial to maintaining hygiene standards and reducing infection within healthcare facilities.

Characterization of β-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR) in a patient with septicemia during long-term vancomycin administration

It was reported that some methicillin-resistant Staphylococcus aureus (MRSA) show resistance to vancomycin (VCM) and beta-lactam antibiotics; thus, they are termed beta-lactam antibiotic-induced VCM-resistant MRSA (BIVR). The VCM resistance of MRSA is induced by the administration of beta-lactam antibiotics, but this phenomenon can be difficult to detect in the clinical laboratory. We detected the BIVR strain in a 64-year-old man who had had a ventilator tube inserted directly into the windpipe during long-term VCM therapy. The patient was diagnosed with MRSA pneumonia and septicemia on July 5, 2007, and sulbactam/ampicillin (SBT/ABPC) was administered for 5 days. However, the fever recurred, and administration of VCM was resumed for 7 days from July 19. Fever developed again, and VCM was administered again for 14 days from September 30. BIVR and VCM-low-sensitive MRSA were isolated from blood on October 18 and 22, although the VCM trough concentration was 10.2 microg/ml. On October 27, we changed to a combination of fosfomycin (FOM) and arbekacin (ABK), and thereafter the fever quickly decreased and the clinical symptoms abated. We isolated five MRSA strains from the blood of the patient, three strains of VCM-sensitive MRSA, one strain of BIVR, and one strain of a VCM-low-sensitive MRSA. The DNA band patterns determined by pulsed-field gel electrophoresis were completely identical except for the VCM-low-sensitive MRSA, which was missing one band. Furthermore, the VCM-low-sensitive MRSA became sensitive to beta-lactam antibiotics. Our results indicate the possibility that long-term VCM therapy is one of the factors that allow BIVR or VCM-low-sensitive MRSA to emerge, and this allows VCM therapy for MRSA to fail.

Vancomycin: Understanding Its Past and Preserving Its Future

The increase in vancomycin use in the 1980s to treat antibiotic-associated colitis and methicillin-resistant Staphylococcus aureus (MRSA) is largely responsible for the appearance of vancomycin-resistant enterococcus, which in turn spawned isolated cases of vancomycin-resistant S. aureus. Perhaps most worrisome to clinicians are strains of MRSA that are heteroresistant to vancomycin; these isolates are difficult to detect. Appropriate use of vancomycin coupled with awareness of infection control measures is paramount to abrogating the emergence of new vancomycin-resistant MRSA organisms and preserving its future efficacy. The continued reliance on vancomycin for the treatment of MRSA infections will depend on whether vancomycin resistance can be minimized. Newer antibacterial agents, particularly those with activity toward MRSA and vancomycin-resistant enterococcus, such as linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline, may take a more prominent clinical role when gram-positive bacteria resistance to vancomycin further escalate.

Prospects for a MRSA Vaccine

Why do we need a vaccine? Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of infection in hospitals and incidence is linked in the public’s mind with hospital cleanliness. In the UK, MRSA causes approximately 7000 cases of bacteremia every year, with a mortality rate of approximately 25%. It probably causes 10–20-times more infections that are not reported, predominantly wound infections and those associated with intravascular access devices. But MRSA is only the tip of the iceberg. The real problem is S. aureus itself, which causes another 11,000 bacteremias with only a slightly lower mortalilty rate. Again, an enormous number of unreported infections also occur. It is well documented that the UK has one of the highest incidences of MRSA per S. aureus infection in Europe (40%); however, it is difficult to know how to interpret this information since we don’t know the incidence of S. aureus infections in other countries. Ideally, S. aureus infections are treated with flucloxacillin, but MRSA are resistant and treated with vancomycin. The first cases of fully vancomycin-resistant MRSA have recently been described. Although several new antimicrobials have been released or are due for release, resistance is already described. Not only do we rely on antimicrobials for treatment, but we are heavily dependent on them for prophylaxis, so that as resistant strains evolve we expect to see infection rates increase. Recent high profile attempts to improve infection control strategies to reduce MRSA incidence in the UK have largely been ineffective. Not only is S. aureus a problem in hospitals, but MRSA strains carrying genes for the Panton–Valentine leukodicin (PVL) are spreading through healthy populations, particularly in the USA [1]. They cause increasing numbers of severe skin and soft tissue infections, as well as fatal hemolytic pneumonia and shock. High-risk groups are those in the military, sports teams, prisoners, intravenous drug users and children. A vaccine to S. aureus infection would therefore be a useful therapeutic and commercially very attractive. However, it is not obvious who should receive a vaccine, especially when tackling hospital infection. Heathcare workers may be a logical step, although this is unlikely to prevent spread of S. aureus via unwashed hands. Immunocompromised patients often respond poorly to vaccines. Colonized patients may be attractive targets, yet few hospitals routinely screen patients on admission to determine who are the carriers, and thus they are rarely offered prophylactic antibiotics that might be just as effective as a vaccine. Despite these limitations, several companies have invested heavily in S. aureus vaccine research.

MRSA—retrospective analysis of an outbreak in the burn centre Aachen

The growing interest in methicillin-resistant Staphylococcus aureus (MRSA) has been caused by its increased appearance in hospital and community populations. In our burn centre, an outbreak of MRSA was noticed during an 8-month period. We were able to isolate MRSA in eight patients. DNA analysis by pulsed-field gel electrophoresis (PFGE) demonstrated the development of five different strains during this period. Only two patients developed an infection caused by MRSA colonisation. The infections were proven by positive blood culture or catheter colonisation. One patient developed a clinical vancomycin-resistant sepsis which was treated successfully with the additional application of Quinupristin/Dalfopristin. This analysis shows that: (1) the development of MRSA in a burn unit is often created in a single patient by long-term antibiotic therapy and not a result of cross-infection, (2) manifest MRSA infection seldom occurs even in colonised burn patients, and (3) a clinically vancomycin-resistant MRSA infection in burn patients can be treated sufficiently with Quinupristin/Dalfopristin.

Nationwide survey shows that methicillin-resistant Staphylococcus aureus strains heterogeneously and intermediately resistant to vancomycin are not disseminated throughout Japanese hospitals.

A total of 6,625 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates obtained from 278 hospitals throughout Japan were obtained between November and December 1997 and were examined for their sensitivities to vancomycin using Mueller Hinton (MH), brain heart infusion (BHI), agar plates, or the broth microdilution method. A concentrated inoculum of an MRSA strain or the use of highly enriched medium, such as BHI medium, allows an individual cell to grow on agar plates containing a vancomycin concentration greater than the MIC for the parent strain. However, cells of the colonies which grew on BHI agar plates containing the higher vancomycin concentrations did not acquire a level of vancomycin resistance greater than that of the parent strain and were not subpopulations of heterogeneously vancomycin-resistant MRSA. There was no significance in the fact that these colonies grew on the higher concentration of vancomycin: none showed stable resistance to vancomycin at a concentration above the MIC for the parent strain, and no cell from these colonies showed a relationship between the MIC and the ability of these colonies to grow on higher concentrations of vancomycin. The vancomycin MIC was not above 2 microg/ml for any of the cells originating from these colonies. No Mu3-type heterogeneously resistant MRSA strains, which constitutively produce subpopulations from MRSA clinical isolates with intermediate vancomycin resistance at a high frequency, were detected. There was a unipolar distribution of the MICs ranging from 0.25 to 2 microg of vancomycin/ml among the 6,625 MRSA clinical isolates, indicating that there was no Mu50-type intermediately vancomycin-resistant MRSA (MIC, 8 microg/ml by National Committee for Clinical Laboratory Standards criteria) among the clinical isolates, and there was no evidence of dissemination of Mu3-type MRSA heteroresistant to vancomycin.

New threats to the control of methicillin-resistant Staphylococcus aureus

Several countries have achieved considerable success in the control of epidemic methicillin-resistant Staphylococcus aureus (MRSA). However, in several hospitals in the UK, MRSA strains of enhanced epidemicity, notably EMRSA-16, are becoming endemic. Our inability to eliminate the cause of a single-strain outbreak is unfamiliar and unnerving. Factors in ‘market-led’ health care delivery that hinder control of MRSA include a shortage of inpatient beds, patients moving from ward to ward, and more mixed-speciality wards. Increasing use of day treatments leaves an inpatient hospital population with more risk factors for infection. Early discharge of infected patients to convalescent homes, or to homes for the elderly, has created a new reservoir of infected and colonized patients. The emergence of high-level mupirocin resistance may soon also contribute to failure of control. The transfer of vancomycin resistance from Enterococcus faecium to a laboratory strain of S. aureus suggests that, especially in hospitals with both vancomycin-resistant enterococci and MRSA, there is the opportunity for the emergence of vancomycin-resistant MRSA for which there may be no effective antimicrobial prophylaxis or treatment. It is increasingly important to persuade hospital managers that even partial control of MRSA, whilst expensive, is still cost-effective and is a quality issue for individual hospitals. The control of EMRSA-16 in one hospital has recently been estimated to have saved more than £629 000 extra costs. MRSA continues to be at the forefront of those organisms that seriously challenge modern technological medicine and surgery.