Infective endocarditis occurs when bacteria enter the bloodstream and travel Bacteria, mycobacteria, or fungi can infect bones by spreading through the bloodstream or, more often, by The bacteria also tend to accumulate on medical devices in the body, such as artificial heart valves or joints, heart pacemakers, and catheters inserted through the skin into blood vessels.
Bloodstream infections: When a catheter that is inserted in a vein has remained in place for a long time. Endocarditis: When people inject illegal drugs or have an artificial heart valve or when a catheter inserted in a vein is infected.
Osteomyelitis: When Staphylococcus aureus spreads to the bone from an infection in the bloodstream or from an infection in nearby soft tissue, as may occur in people with deep pressure sores or foot sores due to diabetes. Lung infection pneumonia Overview of Pneumonia Pneumonia is an infection of the small air sacs of the lungs alveoli and the tissues around them.
Pneumonia is one of the most common causes of death worldwide. Often, pneumonia is the final Many bacteria, viruses, and even fungi There are many strains of Staphylococcus aureus. Some strains produce toxins that can cause staphylococcal food poisoning Staphylococcal Food Poisoning Staphylococcal food poisoning results from eating food contaminated with toxins produced by certain types of staphylococci, resulting in diarrhea and vomiting.
This disorder can be caused by It is caused by toxins produced In addition to the blistered, peeling skin Toxic shock syndrome Toxic Shock Syndrome Toxic shock syndrome is a group of rapidly progressive and severe symptoms that include fever, rash, dangerously low blood pressure, and failure of several organs.
These gram-positive, sphere-shaped coccal bacteria see figure How Bacteria Shape Up cause many disorders This syndrome causes rapidly progressive and severe symptoms that include fever, rash, dangerously low blood pressure, and failure of several organs. Influenza Influenza Flu Influenza flu is a viral infection of the lungs and airways with one of the influenza viruses.
It causes a fever, runny nose, sore throat, cough, headache, muscle aches myalgias , and a general Chronic lung disorders such as cystic fibrosis Cystic Fibrosis CF Cystic fibrosis is a hereditary disease that causes certain glands to produce abnormally thick secretions, resulting in tissue and organ damage, especially in the lungs and the digestive tract Leukemia Overview of Leukemia Leukemias are cancers of white blood cells or of cells that develop into white blood cells.
White blood cells develop from stem cells in the bone marrow. Sometimes the development goes awry A transplanted organ Overview of Transplantation Transplantation is the removal of living, functioning cells, tissues, or organs from the body and then their transfer back into the same body or into a different body.
The most common type of Each ventricle has Heart disorders are Burns Burns Burns are injuries to tissue that result from heat, electricity, radiation, or chemicals.
Burns cause varying degrees of pain, blisters, swelling, and skin loss. Small, shallow burns may need Diabetes mellitus Diabetes Mellitus DM Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar glucose levels to be abnormally high.
Urination and thirst are Major causes are diabetes and high blood pressure Drugs, such as corticosteroids, drugs that suppress the immune system immunosuppressants , or cancer chemotherapy. Many strains have developed resistance Antibiotic resistance Bacteria are microscopic, single-celled organisms.
If carriers take antibiotics, the antibiotics kill the strains that are not resistant, leaving mainly the resistant strains. These bacteria may then multiply, and if they cause infection, the infection is more difficult to treat.
Whether the bacteria are resistant and which antibiotics they resist often depend on where people got the infection: in a hospital or other health care facility or outside of such a facility in the community. Because antibiotics are widely used in hospitals, hospital staff members commonly carry resistant strains. Treatment depends on the type of infection caused by the bacteria. When antibiotics are prescribed, they are selected based on laboratory testing of the bacteria and may involve more than one type.
Staph bacteria are very adaptable, and many varieties have become resistant to one or more antibiotics. However, pH 5. If the pH of growth media is adjusted to pH 4. The same effect is achieved at pH 4. Growth dynamics of S. Growth and fermentative metabolism of lactic acid bacteria, as a permanent component of raw milk microflora, are offered by a wide variety of fermented dairy products.
Besides the most effective inhibitive activity against pathogen and spoilage microorganisms, which includes production of organic acids and subsequent pH decrease, they produce bacteriocins, H 2 O 2 , and aromatic compounds and act as a strong competitor for nutritional factors nicotineamide, biotine or niacine [ 23 , 72 , 73 ].
If there is slow and insufficient acid production in the growth environment, no inhibitive effect is observed. This was the case of Lactobacillus rhamnosus GG and VT1 which did not produce the required amount of lactic acid in milk under aerobic conditions. Despite their inhibitive effect against Candida maltosa and Geotrichum candidum [ 74 ], no inhibition was achieved during the co-cultivation with S. Thus, it is interesting to select an appropriate starter culture of LAB which is able to efficiently inhibit S.
The requirements assigned to a starter culture of LAB include fast growth and survival in dairy environment, rapid production of lactic acid resulting in pH value diminution and no production of toxic or other technologically and sensorially unacceptable metabolites.
The effectiveness of a starter culture of LAB is related to the rate at which it can produce sufficient amounts of lactic acid, predominantly in the first six hours of fermentation. It is connected with the phenomena of the pH lag phase. It is obvious in Fig. The intensity of pH drop is determined by the initial counts of the starter culture, as was confirmed in our co-culture experiments with S.
The following relation between the duration of pH lag phase resulted from the linear regression analysis shown in Fig. It was also observed that during co-cultivation of Fresco culture with S. When the pH started to decrease, the growth of the pathogen stagnated or declined.
This period was influenced by an appropriate amount of starter culture at a specific incubation temperature. The ratio between the initial inoculum of S. It was observed that when the S.
On the other hand, for ratios of or for L. However, our data did not showed a direct relation between the inhibition of S. However, linear regression analysis Fig. Besides initial concentration of LAB, the applied temperature also has a strong effect on the microbial growth dynamics. With an increasing of the incubation temperature, the duration of pH and microbial lag phase is shortened.
On the other hand, the higher the temperature, the higher the growth rates. The combined effect of temperature and the initial Fresco culture is depicted in Fig.
From it, one is able to calculate the necessary addition of Fresco culture and thermal mode during milk or young cheese fermentation to ensure a minimal increase in the numbers of S. According to the EU regulation, the total S. Similarly, also the culture A, which contains Lactobacillus acidophilus , was able to inhibit growth of S. Alomar et al. At an initial concentration of L. Higher temperatures favoured the growth of S. Although acidification plays an important role in S.
If pH and LAB play only a minor role in the inhibition, it can still be hypothesized that the cessation of the growth is due to the accumulation of antistaphylococcal substances produced by the LAB [ 77 ]. Results from literature suggest that S. On the other hand, inhibition of S. Indirect inhibitory effect may also be involved. The availability of nutrients may trigger other mechanisms, leading for instance to the secretion of metabolites, peptides or signalling molecules, which would in turn be responsible for the inhibitory effect of LAB [ 60 ].
Dependence of increase in S. Fermentation of the lump cheese relies on native mesophilic lactic acid bacteria LAB such as Lactococcus lactis , Enterococcus faecalis , Lactobacillus casei , Lb. During ripening, the essential role is played by the milk mould Geotrichum candidum and oxidative yeasts of the genera Torulopsis , Candida and Kluyveromyces [ 1 , 3 ]. Generally, cheeses are considered as one of the safest foods currently consumed.
However, pathogenic bacteria which can be transmitted by dairy products cannot be underestimated. Historically, there have been several outbreaks related to the consumption of cheeses. The predominantly responsible organisms Listeria monocytogenes , Escherichia coli , Salmonella spp. The sources of their contaminations were raw milk, inadequately pasteurized milk, or post-pasteurization contaminated milk [ 47 , 51 , 78 , 79 ]. In this context, microbiological specifications related to the finished cheeses made from raw milk defined by the Commission Regulation No.
They comprise of absence Salmonella spp. Despite the raw milk origin and substantial proportion of raw milk cheeses containing enterotoxigenic S. The safety and quality of fermented original cheeses manufactured from raw milk at a primary level is generally determined by various specific hygienic, technological, and intrinsic and extrinsic environmental factors. The factors which contribute to the safety of cheeses with respect to pathogenic bacteria include milk quality, native lactic acid bacterial growth during cheese manufacture, pH, salt, environmental conditions and chemical changes during ripening.
However, the most important role during fermentation is played by metabolism of the LAB participating in effective competition with pathogenic and spoilage microorganisms and subsequently in inhibition of undesirable microorganisms.
According to our investigations of eight products manufactured under upland farm conditions, the acidification of the curd started after a h period and went on intensively for 20 h. Thus, a level of acidity equivalent to pH of 5. Such a fairly long time permits to the growth not only LAB but also of undesirable bacteria, including S.
Within these field trials, the initial numbers of S. The first 24 h of the process of making raw milk cheese appeared to be critical for S. In cheeses with relatively slow acidification during the first 6 h, pH has no effect on the initial growth phase of S. High pH value in the fresh cheese suggests a weak lactose fermentation ability by the non-starter LAB [ 7 , 58 , 76 ].
In order to prevent S. As our previous experiments in model milk media confirmed, the Fresco culture is effective in the S. As seen in Fig.
Such a short pH lag phase is crucial in pathogen growth inhibition during cheese manufacture, as has already been mentioned. Higher diminution of pH during the first 6 hours of fermentation means lower S. The S. An increase in microbial counts in the first 24 h is a normal process in cheese making. This is partly due to the physical retention of microorganisms in the coagulum and also due to the microbial multiplication during coagulation and whey drainage [ 7 , 80 , 81 ].
In contrast to cheese without the addition Fresco starter, the S. Consumption of such a cheese might represent a potential threat of food poisoning outbreak if the enterotoxigenic strains are present. In order to keep the numbers of S. These initial counts would be accompanied with the suitable timing of pH decrease down to pH 5.
The addition of an appropriate amount of mixed mesophilic LAB culture, which produces inhibitory substances, provides opportunities to add additional barriers to the growth of bacterial pathogens. This assumption was also confirmed by some other authors. Olarte et al. In cheese without added starter culture, S. A rapid decrease in pH values from 6. From an initial average density of 1. In those cheeses S. Such acidic conditions contributed to the decrease in S. In raw milk cheeses collected by Jakobsen et al.
The highest S. Nevertheless, none of the sample exceeded counts higher than 5 logs and so it was concluded that S. A correlation between the contamination level of the milk and contamination level of h old cheeses was noticed.
However, most available data are from high-income countries for example, Japan, South Korea and Singapore , with limited information from other nations. High methicillin resistance rates are thought to be related to widespread inappropriate antimicrobial use for example, self-medication and over-the-counter use as well as high population density facilitating rapid transmission of multidrug-resistant organisms Nevertheless, some countries in Asia for example, Taiwan 39 that experienced a peak in HA-MRSA prevalence in the late s have shown declining prevalence since the early s In Australia, among health-care-associated S.
MRSA prevalence data from Africa are variable in coverage and quality. Published data are available for South Africa, Nigeria and countries from the Mediterranean basin, but there is a paucity of data from other nations Most data are also from single-centre studies, and information from broader surveillance systems is lacking.
In addition, most studies have relied on phenotypic methods to identify MRSA, and these tests might be less reliable than genotypic methods depending on the choice of antibiotic used to detect MRSA Differences in the availability and use of antimicrobials, incidence of HIV infection a risk factor for MRSA colonization 46 and infection control practices could potentially account for some of the variation between countries.
Less commonly, infection can occur in the absence of known S. The principal site of S. Longitudinal studies have identified three temporal patterns of S. Continuous S. Similar results were found by other studies Studies exploring specific host polymorphisms in genes involved in the inflammatory response 51 indicate that there are underlying host factors that determine the carriage status. However, the precise nature of these underlying factors is not completely understood.
For MRSA in particular, the duration of colonization is variable, and reported estimates could be biased by antibiotic treatment, which can shorten the duration of colonization. Besides host factors, factors associated with the pathogen itself as well as the nasal microbiota can influence host carrier status. Dynamics of colonization. During S. Of these components, S. A wild-type strain and its single locus clfB knockout variant were inoculated into the nose; the knockout variant was cleared significantly more rapidly than the wild-type strain.
However, ClfB-deficient strains can still interact with nasal cells, indicating that there are several independent microbial surface components that play a part in colonization It must also be noted that only one strain was used in this study. Besides host and pathogen factors, the interaction of S. Studies of the nasal microbiota have shown that the presence of some species correlates with the presence or absence of S. The organisms of the nasal microbiota are in competition with each other in several ways.
For example, they compete for adhesion sites and nutrients: there are low amounts of nutrients in the human nose. However, no difference in nutrient levels has been observed between carriers and non-carriers Microbiota species also compete by antibiosis, that is, certain strains can produce antimicrobial molecules that inhibit their microbial competitors.
In humans, nasal colonization with S. These findings are certainly interesting but explain only a minority of carriage patterns, as S. Finally, S. Many studies support the role of these mechanisms in the interactions between S. Many virulence genes are found on mobile genetic elements; thus, their combination differs substantially between clones and even between closely related strains. The potential association of specific virulence factors with certain types or aggressiveness of S.
Furthermore, many virulence factors cannot be investigated in animal models because they are human-specific This section focuses on the most prominent virulence mechanisms and typical routes of invasion. Initiation of infection. The capacity of S. The subsequent influx of polymorphonuclear leukocytes PMNs is manipulated by S. Staphylococcus aureus can also in part regulate polymorphonuclear leukocyte PMN influx in subtle ways involving activators formylated peptides and phenol-soluble modulin PSM peptides and inhibitors for example, chemotaxis inhibitory protein of S.
PSM peptides also promote the release of pro-inflammatory lipoproteins, the major S. The capacity of PMNs, which are found in high numbers in an abscess, to eliminate S. The bacteria can also inhibit the complement signalling pathway by small secreted inhibitors such as staphylococcal complement inhibitor SCIN , fibrinogen-binding protein Efb , extracellular complement-binding protein Ecb or staphylococcal superantigen-like protein 7 SSL7 , among others.
Phagocytosed bacteria can survive within the PMNs by producing catalase, superoxide dismutase [Mn] 1 SodA , staphylococcal peroxidase inhibitor SPIN , staphyloxanthin against the bactericidal oxidative burst generated by the PMNs 72 and extracellular adherence protein Eap against elastase 76 , and the cell envelope modifications mediated by multiple peptide resistance factor MprF and the D -alanine transfer proteins DltA, DltB, DltC and DltD protect against defensins.
APC, antigen-presenting cell. Abscess formation. The S. Bacteria that are phagocytosed by PMNs can survive not only by counteracting PMN killing mechanisms 72 , 76 , 77 but also by gradually destroying them with the help of cytolytic toxins.
The massive inflammation elicited by activated or necrotic PMNs is further increased by S. Systemic infection. Abscesses might be disrupted at later stages, releasing pus and live bacteria either towards the skin surface to promote pathogen transmission or towards the bloodstream to cause bacteraemia Fig. Endovascular S. The agglutinating activity of coagulases is thought to contribute to systemic blood coagulation, and massive release of microorganism-associated molecular pattern molecules along with superantigen toxin-induced cytokine storms leads to fulminant systemic inflammation, sepsis and multi-organ failure if the endovascular spread of the bacteria cannot be contained Regulation and adaptation.
Most of the S. Accordingly, Agr is not very active in many HA-MRSA clones, which produce lower amounts of toxins but higher levels of adhesins and often cause bacteraemia via infected catheters or implanted medical devices. High virulence seems to even be detrimental for S. Elucidating virulence mechanisms whose inhibition would render S. A crucial event in the evolution of S. Twelve known SCC mec types I—XII have been identified and are classified according to the type of cassette chromosome recombinase ccr complex and the class of the mec complex Table 2.
A variant of mecA , named mecC , was identified in several S. In , plasmid-borne methicillin resistance based on mecB has been identified in S. Antibiotics have diverse mechanisms of action and target different bacterial structures or metabolic pathways. Existing antibiotic options are in green, new antibiotics approved and on the market are in blue and antibiotics in the pipeline are in orange.
Figure adapted from Ref. The primary control of the expression of mecA depends on the regulators encoded by mecI , mecR1 and mecR2 Refs 96 , 97 and on the regulators of the expression of the genes blaZ , blaI and blaRI Ref. In addition, a surprisingly large number of genes — auxiliary or fem genes — has a profound influence on the resistant phenotype Three lines of evidence show that the level of mecA transcription is not predictive of the degree of methicillin resistance.
First, the stringent stress response that is, the bacterial reaction to different stress conditions, such as amino acid, fatty acid and iron limitation and heat shock induced by the antibiotic mupirocin triggers an increase in PBP2a activity without affecting mecA transcription Second, inactivation of vraS a member of the two-component regulatory system involving sensor protein VraS and response regulator protein VraR VraS—VraR involved in the control of the cell wall peptidoglycan biosynthesis induced mecA transcription but did not increase the level of PBP2a activity Third, the chaperone foldase protein PrsA alters the levels of properly folded PBP2a in the membrane and, therefore, methicillin resistance without affecting mecA transcription The crucial role of the stringent stress response in mecA expression has been demonstrated using different experimental approaches 99 , Of note, over the years, some MRSA clones have also acquired resistance to vancomycin , the first-line treatment of invasive MRSA infections in hospitalized patients since the s Box 1.
Vancomycin has been the drug of choice for treating invasive methicillin-resistant Staphylococcus aureus MRSA infections in hospitalized patients since the early s. However, over the years, MRSA has acquired resistance to vancomycin Vancomycin intermediate-resistant S. The VISA phenotype results from mutations acquired during antibiotic therapy Despite its low vancomycin minimum inhibitory concentration MIC; the lowest concentration of an antibiotic that prevents bacterial growth of 3—8 micrograms per millilitre, VISA has been associated with treatment failures The clinical relevance of hVISA has been extensively debated.
Vancomycin failure has been reported for some hVISA or VISA infections; nevertheless, several studies have failed to detect an association between infection with hVISA and poor outcomes with therapy with vancomycin , Similarly, if reduced susceptibility to daptomycin is observed alongside reduced vancomycin susceptibility, then a combination of or use of a single agent among the following is recommended: quinupristin—dalfopristin, trimethoprim—sulfamethoxazole, linezolid or telavancin Vancomycin-resistant S.
Vancomycin resistance in VRSA is mediated by the vanA gene, which is believed to have been transferred from Enterococcus faecalis on the plasmid-borne transposon Tn Ref. VRSA strains are mostly found in diabetic wounds infected by both vancomycin-resistant enterococci and S.
VRSA has remained extremely rare, possibly owing to the fitness costs associated with acquisition of vancomycin resistance MRSA can cause a wide range of infections, such as SSTIs, pneumonia, osteoarticular infections, toxic shock syndrome a rare, potentially life-threatening complication of infection with certain types of bacteria, including S.
HA-MRSA is a cause of bacteraemia, pneumonia and, less commonly, SSTIs particularly related to invasive procedures, for example, at surgical wounds or vascular access sites in hospitalized patients The organism is often associated with invasive devices, such as intravascular catheters, endotracheal tubes and urinary catheters, probably owing to its capacity to form and survive in biofilms Individuals who have had lengthy hospitalization, ICU admission, residency in a nursing home, antibiotic exposure particularly to cephalosporins and fluoroquinolones, leading to antibiotic selection pressure , surgery, haemodialysis, chronic wounds or indwelling invasive devices have an increased risk of infection with HA-MRSA Fulminant infections with CA-MRSA strains have been reported, such as necrotizing pneumonia and necrotizing fasciitis a rapidly progressive infection of the fascia with secondary necrosis of the subcutaneous tissues , However, the presence of PVL varies from strain to strain, suggesting that other virulence factors contribute 7.
Populations or settings in which outbreaks of CA-MRSA infection have been reported include sports teams, military personnel and prisons , On the basis of these observations, close contact with MRSA carriers as occurs in households or other communal living environments , shared equipment or personal items and skin trauma including trauma caused by injecting drug use or body shaving might be associated with an increased risk of CA-MRSA infection.
LA-MRSA has been associated with localized infections, such as SSTIs including abscesses and wound infections and otitis, as well as severe and invasive infections, such as bacteraemia, pneumonia, osteoarticular infections and endocarditis LA-MRSA predominantly colonizes and infects individuals who have direct contact with livestock including cattle, horses, chickens and turkeys but particularly pigs and their household members through transmission within the household However, there are reports of LA-MRSA in individuals with no connection to livestock, and in these cases, spread via environmental contamination or, less commonly, food-borne transmission has been postulated Microbiological specimens from which MRSA can be isolated can be broadly classified into clinical and screening samples.
Clinical samples for example, specimens of purulent discharge, deep tissues, sputum and blood are collected from individuals with symptoms or signs to investigate for active infection, whereas screening samples for example, nasal, perineal and throat swabs are obtained to detect asymptomatic colonization.
An array of phenotypic and non-phenotypic methods can be used to detect MRSA directly from clinical or screening samples or to identify MRSA from presumptive staphylococcal colonies isolated from clinical samples. Phenotypic methods are usually preferred for clinical diagnostics. Phenotypic methods. Pure S. Initially, oxacillin was utilized as the marker antibiotic to detect MRSA; however, CLSI now recommends cefoxitin, as it is a better inducer of mecA and mecC than oxacillin and results in a clear recognizable phenotype This is because the mecA encoded PBP2a is less efficient at crosslinking the pentapeptide chains of the cell wall peptidoglycan during cell wall synthesis, resulting in slower growth of the resistant isolates.
This phenomenon leads to a heteroresistant population, wherein cells exhibit different levels of resistance and some are phenotypically susceptible The above-mentioned susceptibility testing guidelines enable the slower growing MRSA subpopulation to reach detectable levels in a heteroresistant population.
Rarely, MRSA may present with phenotypic sensitivity to cefoxitin and oxacillin and require an overnight exposure to low concentrations of cefoxitin to exhibit resistance In this case, the presence of inducible mecA should be considered. Methicillin resistance in S. Moreover, several automated instruments performing identification and antimicrobial susceptibility testing of staphylococci have shown high sensitivities and specificities for the MRSA strains tested reviewed in Ref.
For direct phenotypic detection of MRSA from positive blood cultures, there is renewed interest in refining bacteriophage-based assays. The assay detects the amplification of S. Multicentre evaluation of this assay on 1, blood cultures showed Non-phenotypic methods. One of the most promising non-genotypic techniques for direct identification of pathogens from positive blood cultures is matrix-assisted laser desorption-ionization time-of-flight mass spectrometry MALDI-TOF MS Identification is based on the comparison of the protein profile obtained by mass spectrometry from a bacterial or fungal sample with a database of profiles obtained from several characterized microorganisms.
However, as the performance of MALDI-TOF MS largely depends on a microorganism's purity and quantity, bacterial enrichment and purification procedures are required from positive blood cultures, which contain high concentrations of interfering non-microbial material A retrospective study of cases of S.
Although the length of hospitalization and rates of adequate empirical antibacterial therapy were similar in the two groups, optimization of therapy occurred more frequently in the group assessed by MALDI-TOF MS Results are obtained in approximately 1. The application of WGS to bacterial pathogens heralded the single most important advance in diagnostic microbiology and surveillance since in vitro culture.
However, direct applications of WGS in diagnostic microbiology remain limited, primarily because of the technological constraints in obtaining results within a time frame that can influence patient care and the need for standardized protocols and automated data interpretation. The introduction of the third generation of sequencers such as the Oxford Nanopore MinION by Pacific BioSciences and Oxford Nanopore, Oxford, UK has resulted in longer reads obtained sequence lengths that can span repeat regions in the bacterial sequence and enable complete bacterial genome assembly, as well as an increased portability of the machinery and a potential reduction in error rates.
An important benefit afforded by the Oxford Nanopore MinION sequencer is that sequencing data can be analysed in real time and could lead to strain identification within 30 min and an antibiotic-resistance profile prediction within 10 hours after the start of a run , making this assay potentially useful for clinical diagnostics. The utility of WGS has been well demonstrated for studying antibiotic resistance and the population biology of MRSA and has also led to many useful insights regarding transmission of MRSA during hospital outbreaks and in community settings Screening measures and their effectiveness are discussed in the Prevention section below.
Since the introduction of the first MRSA chromogenic medium that is, a medium containing synthetic chromogenic enzyme substrates; in the presence of the specific target enzyme, the chromogenic substrate is processed and results in a corresponding bacterial colony of a specific colour, thereby enabling pathogen recognition , these media have undergone rapid improvements in terms of sensitivity of the chromogen and the antibiotics used , They have become the primary rapid diagnostic assays utilized for active surveillance for MRSA colonization as well as for patient diagnostics since they were introduced in the s Development of automated colony scoring that could further increase specificity and reduce turnaround time is also being attempted Application of real-time PCR-based assays for MRSA screening from nasal swabs can decrease turnaround time to 1—2 hours, whereas the results of chromogenic media-based tests can take a minimum of 14—18 hours without confirmatory testing and, therefore, might not always be useful to guide clinical decisions.
A patient bed day represents a unit of time during which a patient occupies a bed and stays overnight in a health-care facility; thus, 50 patients in a hospital over a period of 1 day would represent 50 patient bed days.
However, a major study in 13 ICUs in eight European countries did not find any positive effect of screening using PCR-based tests versus chromogenic media in the acquisition and transmission rates of multidrug-resistant bacteria including MRSA, vancomycin-resistant enterococci and highly-resistant Enterobacteriaceae Similarly, a UK-based study assessing screening by real-time PCR-based tests versus slower laboratory-based methods MRSA-selective broth and chromogenic medium reported a significant reduction in turnaround times from MRSA control interventions have been widely implemented across health-care facilities.
These interventions aim to limit the emergence of MRSA by facilitating judicious use of antimicrobial agents including introducing restrictions on their prescription , control the reservoir of patients who are carriers, prevent MRSA transmission between patients and prevent the development of infection in carriers.
Several measures are usually required to successfully prevent transmission and infection with MRSA Decolonization, an important control intervention for which there is growing evidence, is discussed in the Management section. Hand hygiene. Hand hygiene, with alcohol-based hand rub or soap and water, aims to reduce MRSA spread via this route. Indeed, the WHO has identified hand hygiene as an important factor in providing safe patient care and has issued detailed instructions regarding appropriate hand hygiene practices among health-care workers , The effectiveness of improving compliance with hand hygiene among health-care workers in MRSA control has been demonstrated at local as well as national levels , For example, the roll out of a national hand hygiene programme in England and Wales from late was associated with a fall in the incidence of MRSA bacteraemia from 1.
Although the hand hygiene campaign was implemented with other national infection control initiatives, the higher procurement of alcohol hand rub during the campaign was independently associated with reduction in the incidence of MRSA bacteraemia after adjustment for all other interventions Active surveillance.
Through screening methods, active surveillance programmes can identify this large asymptomatic reservoir of carriers and direct interventions such as topical decolonization to reduce transmission or infection risk. Universal MRSA screening has been one of the most controversial areas in infection control since the s, with some studies showing that it is effective in reducing MRSA-associated disease , whereas other studies found it ineffective , Importantly, recent data also show that universal screening is unlikely to be cost-effective, particularly in settings with low or decreasing MRSA prevalence On the basis of this accumulating evidence, many health-care facilities have now abandoned universal MRSA screening.
We suggest, however, that changes in practices should be based on careful consideration of local MRSA epidemiology and the vulnerability of the patient population.
However, a long turnaround time for screening results a mean of 5. Contact precautions and isolation. In many facilities, health-care workers use contact precautions use of disposable gowns and gloves when caring for patients with MRSA colonization to reduce MRSA transmission associated with contamination of hands and clothing.
Although the evidence for this intervention has previously been of low quality, there is now more robust data suggesting that this practice is associated with reduction in MRSA acquisition It is also widely recommended that patients with MRSA colonization are isolated in single rooms. Experts have called for a review of this practice and for guidelines to highlight the uncertainties regarding its value The approach to the management of MRSA varies in different geographical regions depending on local MRSA prevalence and availability of antimicrobials, particularly the newer agents.
MRSA colonization is associated with an increased risk of infection and contributes to transmission. Both MRSA colonization on admission as well as acquisition during hospitalization are associated with an approximately tenfold increased risk of subsequent infection Thus, decolonization can contribute to MRSA control by reducing transmission and infection risk.
Most decolonization strategies use topical agents applied to the nostrils, the principal site of colonization Mupirocin pseudomonic acid A, which inhibits bacterial isoleucyl tRNA synthetase, preventing protein synthesis is the principal agent and is often combined with chlorhexidine bathing Although mupirocin is the cornerstone for eradication of S.
Alternative agents are being studied, but to date, experience with these agents is limited Thus, it is recommended that mupirocin is used judiciously and that the emergence of resistance is monitored Ongoing research into the development and evaluation of new agents that can be effectively used for decolonization is also needed. Short-term decolonization. Decolonization is most commonly used as a protective strategy during relatively short periods of increased risk of infection, for example, during the peri-operative period or ICU stays.
Topical mupirocin to the nares and chlorhexidine body washing before surgery for known S. However, this study was performed in the Netherlands, a country with low MRSA prevalence, and the effects of this short-term decolonization strategy might be different in settings with high MRSA prevalence.
The results of short-term decolonization interventions in the ICU setting have been variable. A large cluster-randomized trial compared three strategies : screening and isolation of MRSA carriers no decolonization ; a combination of screening, isolation and decolonization with mupirocin and chlorhexidine bathing of MRSA carriers targeted decolonization ; and decolonization of all patients universal decolonization.
No significant differences in MRSA colonization and infection rates were found with the three strategies. However, bloodstream infections from any pathogen were significantly lower in the universal decolonization group.
This may have been the result of universal chlorhexidine bathing rather than mupirocin. The authors concluded that universal decolonization was the best approach, as it reduced infections overall without the need for screening.
However, as widespread use of topical antibiotics might lead to an increase in drug resistance, their use should be coupled with monitoring for resistance Permanent decolonization. In some situations, permanent MRSA eradication is pursued.
For example, the Dutch protocol distinguishes between uncomplicated and complicated carriers on the basis of MRSA strain and host characteristics, as well as colonization site, as treatment failure is three times more likely in individuals with throat colonization than in those without throat colonization Many other clinical trials evaluating permanent decolonization strategies have been conducted under real-life conditions, with rather disappointing results because of a high rate of endogenous recolonization Empirical treatment and SSTIs.
The choice, route of administration and duration of antibiotic therapy are determined by the site and severity of infection. Treatment should then be adjusted on the basis of subsequent results of cultures and susceptibility testing. Intravenous vancomycin, daptomycin or linezolid can be used for severe SSTIs. Oral therapy as a rule should be avoided in the initial treatment of severe infections. Clindamycin, trimethoprim—sulfamethoxazole and doxycycline are alternative choices for the treatment of mild to moderate SSTIs, depending upon the antibiotic susceptibility testing.
For uncomplicated skin abscesses, the use of clindamycin or trimethoprim—sulfamethoxazole in conjunction with incision and drainage has been shown to improve clinical cure rates in the emergency department and other outpatient settings , Systemic and severe infections. The current recommendations for clinical management of severe MRSA infections include intravenous vancomycin or daptomycin for bacteraemia and intravenous vancomycin or linezolid for hospital-acquired pneumonia For severe infections, oral linezolid should not be used for initial therapy.
However, when the patient has become stable and can tolerate the oral route, a switch to oral linezolid is recommended. In the setting of infection related to the presence of a medical device such as central venous catheters , successful treatment usually requires removal of the device when possible Glycopeptides such as vancomycin and teicoplanin have been the mainstay of intravenous treatment for MRSA infections.
Vancomycin remains the cornerstone of empirical treatment for systemic infections potentially caused by MRSA, first because of its safety profile and second owing to lack of other fully approved alternatives , Teicoplanin is also commonly used in Europe and has been found to be non-inferior to vancomycin in terms of all-cause mortality, with an improved safety profile, although few patients with serious infections were studied Table 3.
However, higher trough concentrations are associated with an increased risk of nephrotoxicity and no clear improvement in outcome. Finally, vancomycin is administered in a continuous infusion instead of intermittent injections in some European countries However, there are insufficient data to make recommendations regarding this protocol Switching to daptomycin therapy, on the basis of the daptomycin MIC, should be done as early as possible once an elevated vancomycin MIC is confirmed.
Alternative anti-MRSA antibiotics are increasingly being used, but it is important to note that they can have adverse effects, particularly linezolid Table 3. Of note, although reports of vancomycin failure have emerged for vancomycin intermediate-resistant S. Combination therapy. The increased duration of bacteraemia is associated with complications such as attributable mortality, complicated infection, embolic stroke or recurrent S.
Combination therapy to treat S. However, evidence that combination therapy improves outcomes is lacking Several studies have demonstrated in vitro synergy between vancomycin and gentamicin against many MRSA isolates , However, this combination seemed to be numerically inferior to daptomycin alone in the treatment of MRSA bacteraemia and endocarditis in a randomized trial Thus, because even low dose gentamicin 1 milligram per kilogram every 8 hours for a short duration has been associated with substantial nephrotoxicity and because the clinical effectiveness of vancomycin plus gentamicin is not confirmed, combination therapy with aminoglycosides is difficult to justify Vancomycin and rifampicin combinations have also been studied, particularly in the context of biofilm infections However, the addition of rifampicin to vancomycin is not recommended for MRSA bacteraemia or native valve endocarditis In addition, a randomized controlled trial evaluating adjunctive rifampicin in S.
However, sufficient clinical evidence in favour of this combination is lacking. In the CAMERA-1 trial comparing vancomycin versus vancomycin plus flucloxacillin , the mean time to resolution of bacteraemia primary outcome in the combination group was 1.
Ceftaroline plus daptomycin could be another option for refractory staphylococcal bacteraemia. Ceftaroline offers dual benefit via synergy with daptomycin and sensitization to cathelicidin antimicrobial peptide-derived LL, a peptide of the host innate immune response; sensitization to cathelicidin could attenuate the virulence of the pathogen see New drugs and current pipeline.
Other combinations for example, daptomycin and rifampicin might be promising options in biofilm-related infections Other considerations. In contrast to many other bacterial infections, S. In cases of documented bacteraemia, the recommended minimum duration of treatment is 14 days , as short-course therapy is currently not considered to be safe and effective. Options for salvage therapy, based on low-quality data, include linezolid, trimethoprim—sulfamethoxazole, ceftaroline, quinupristin—dalfopristin and telavancin.
Tigecycline should be avoided, as it is bacteriostatic against MRSA and has a large volume of distribution with high concentrations in tissues but low concentrations in serum No data in MRSA bacteraemia are yet available for other recently approved agents for example, ceftobiprole, dalbavancin, oritavancin or tedizolid.
Several new agents have been approved for the treatment of SSTIs and in some cases for pneumonia Fig. However, the efficacy and safety of these antibiotics for invasive infections, for which there is a real need, have largely not been demonstrated.
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