Methicillin-resistant s. Aureus (mrsa)
INTRODUCTION
Methicillin-resistant S. aureus (MRSA) is a problem in many hospitals whose outbreak in wards and theatre patients lead to significant morbidity and mortality. It is a special type of S. aureus with plasmid-mediated resistance to Methicillin.
MICROBE DESCRIPTION
Staphylococci generally stain darkly gram positive. They are round and tend to occur in branches like grapes. They are fastidious requiring various amino acids and other growth factors. They are routinely cultured on enriched media containing broth and/or blood. They are true facultative anerobes and produce catalase which distinguished them from the catalase-negative streptococci.
The most virulent species is S. aureus, almost all isolated organisms secrete coagulase which distinguishes them from the non-pathogenic staphylococcus. Staphyloccus aureus is found in the nose of 10-30% of normal people but occasionally on healthy skin. It is a common cause of infection in the community and in the hospital. Most infections are sporadic but occasional outbreaks occur.
Methicillin-resistant S. aureus (MRSA) is no different from the others except for its resistance to methicillin and similar antibiotics. The resistance is usually plasmid-mediated. The spread of plasmids between different strains of Staphylococcus aureus is facilitated by transducing phages.
PATHOGENESIS OF METHICILLIN-RESISTANT S. AUREUS (MRSA) INFECTIONS
Generally, significant host compromise is required for S. aureus infection such as break in the skin or insertion of a foreign body, an obstructed hair follicle or a compromised immune system. S. aureus disease may be largely or wholly the result of actual invasive infection, overwhelming host defense mechanisms, and the production of extracellular substances which facilitate invasion; or as a result of toxins in the absence of invasive infection or a combination of the two factors.
DISEASES CAUSED BY STAPHYLOCOCCAL ORGANISM
Diseases caused by staphylococcal organism include:
· Skin infections including boils, carbuncles, breast abscesses, surgical wound infections, neonatal skin sepsis and rare toxic complications such as toxic epidermal necrolysis and toxic shock syndrome
Deep tissue infections including pneumonia, osteomyelitis, septic arthritis and endocarditis. Nosocomial Pneumonia is caused by different pathogens, the aerobic gram-negative bacilli (i.e., excluding H influenzae). Pseudomonas aeruginosa is not the most common cause of NP but is the most important organism in terms of mortality and morbidity. Staphylococcus aureus (i.e., methicillin-susceptible S aureus [MSSA], methicillin-resistant S aureus [MRSA]) and anaerobic organisms are not significant contributors to NP.
· Septicemia and complications of septicemia such as disseminated intravascular coagulation, endocarditis and metastatic abscesses.
· Food poisoning as seen in staphylococcal enterocolitis
Penicillin, cloxacillin, erythromycin, lincomycin, fusidic acid, vancomycin are antibiotic that have potent antistaphylococcal effects. However multiple antibiotic resistance to two or more different antibiotics may occur, especially in the hospital particularly in the case of
Methicillin-resistant S. aureus (MRSA).
Methicillin-resistant S. aureus (MRSA) outbreaks have become a serious problem, particularly in high-risk patients such as intensive care units, cardiothoracic and vascular surgery units, and orthopedic units carrying out prosthetic joint surgery. These are numerous routes for Methicillin-resistant S. aureus (MRSA] spread by cross-infection. . However, in the majority of cases, the source of the infection in the ward is due to usually a patient with an established wound infection.. In an operating theatre outbreak, the source is usually a member of the surgical team, the source is usually a member of staff who has either been infected or is a carrier.
Virtually all community- and hospital acquired S. aureus infections are now resistant to Penicillin G due to penicillinase-encoding plasmids or transporons. This has required the replacement of the initial agent of choice, penicillin G, by beta-lactamase-resistant penicillins such as methicillin or oxacillin. However, increased use of methicillin and related antibiotics has resulted in Methicillin-resistant S. aureus (MRSA)
HOSPITAL-ACQUIRED METHICILLIN-RESISTANT S. AUREUS (MRSA)
Hospital-acquired Methicillin-resistant S. aureus (MRSA): more than 50% of S. aureus isolates have been found to be Methicillin-resistant S. aureus (MRSA). This resistance is as a result of chromosomal acquisition of the gene for a modified penicillin-binding protein [PBP], PBP-2a. This proteins codes for a new peptidoglycan transpeptidase with a low affinity for all currently available beta-lactam antibiotics and thus renders infections with Methicillin-resistant S. aureus (MRSA) unresponsive to beta-lactam therapy. Compared with Methicillin-sensitive S. aureus (MSSA), infections are associated with worse outcomes, including longer hospital stays and duration of mechanical ventilation and higher mortality rates. Methicillin-resistant S. aureus (MRSA) strains also frequently resistant to many other antibiotics.
National Nosocomial Infection Surveillance (NNIS) surveys indicate that S aureus causes approximately 20% of the infections. These surveys are based on endotracheal aspirate cultures. They reflect staphylococcal colonization of the hospitalized patient. If S aureus caused by MRSA or MSSA indeed were responsible for 20% of the patients diagnosed with Nosocomial Pneumonia NP, then this characteristic picture would occur in 1 of 5 patients, which is not the case. In fact, S aureus NP is so rare that it is listed as a reportable disease. Most patients with S aureus pneumonia show symptoms of fever, pulmonary infiltrates, and leukocytosis, with S aureus cultured from the airways and peripheral blood cultures. Patients with S aureus NP do not meet the histologic or radiologic criteria for S aureus pneumonia. A blood culture that is positive usually is caused by contamination during the blood culture collecting process, e.g., by S aureus on the skin or from an IV line infection unrelated to the pulmonary process.
COMMUNITY-ACQUIRED METHICILLIN-RESISTANT S. AUREUS (MRSA)
Community-acquired Methicillin-resistant S. aureus (MRSA) infections were documented in the mid-90s occurring in individuals who have no previous risk factors for Methicillin-resistant S. aureus (MRSA) infections such as exposure to hospital. The most common clinical manifestation of this kind of Methicillin-resistant S. aureus (MRSA) infection are skin and soft tissue infections such as cellulitis and abscesses. Less commonly, they cause septicemia, osteomyelitis and necrotizing pneumonia. Community-acquired Methicillin-resistant S. aureus has a characteristic pattern of DNA fragments obtained upon enzymic cleavage and electrophoresis, and it produces specific toxins,. It also has a unique antibiotic resistance pattern; this implies that it is sensitive to certain antibiotics which are not useful in hospital acquired Methicillin-resistant S. aureus infections. These antibiotics are ciprofloxacin and clindamycin.
MRSA is becoming established outside of the hospital. Besides, enterobacteriaceae and P aeruginosa are becoming more resistant to multiple antibiotics. Knowing the resistance patterns in the community, as well as in the hospital, is most important.
RISK FACTORS
Predisposing host factors to staphylococcal infections include diabetes mellitus, neutropenia, hypogammaglobulinaemia, and rare phagocyte defects such as seen in chronic granulomatous disease. Risk factors that have been associated with MRSA colonization or infection include age, coma, invasive procedures, and extended hospitalization. Methicillin-resistant S aureus (MRSA) is more prominent in the diabetic population. MRSA is becoming more common, especially in persons with chronic wounds and in patients who are diabetic. A recent study has demonstrated that MRSA occurs in up to 25% of diabetic foot infections involving S aureus. A higher incidence of MRSA exists in patients who have been on prolonged ciprofloxacin therapy. The MRSA often only colonizes the superficial surface of the ulceration and should not be treated as the infectious agent.
INCIDENCE
Increasing incidence has been reported in hospitals all over the world. These Methicillin-resistant S. aureus (MRSA) are particular resistant to methicillin and other antibiotics have been reported. In fact, the In Japan and the USA, a few strains of Methicillin-resistant S. aureus (MRSA) have now been reported to be resistant to vancomycin, the drug of choice against the organism. The incidence of MRSA colonization and subsequent infection has increased dramatically in the last decade, primarily because of antibiotic selective pressure in critically ill hospitalized patients.
INVESTIGATIONS
Swabs of the potential carrier sites of ward or theatre staff may be collected and swabs of the wounds of all patients in the ward in a s suspected outbreak of Methicillin-resistant S. aureus (MRSA). Besides, swabs of infected/suspected sites can be taken for microscopy, culture and sensitivity. Blood culture is also indicated.
TREATMENT
Imagine this case: Methicillin-resistant S. aureus (MRSA) was isolated from 7 patients in a 14-bed intensive care unit. All patients were isolated and the unit closed to any more admissions. Why were these steps taken? The simple answer is to control MRSA because although it is not inherently more virulent than other staphylococci but because the alternative for treatment of MRSA is vancomycin, an expensive and potentially toxic antibiotic.
Oxacillin- and methicillin resistant S. aureus (MRSA) has been rapidly increasing in incidence. MRSA and methicillin-sensitive S. aureus (MSSA) coexist in heterologous populations. Treatment of a patient harboring this heterologous population may provide a selective environment for the MRSA. Prior to changing therapy, the susceptibility of the isolate should be determined.
Vancomycin (Lyphocin, Vancocin, Vancoled) — A bacteriocidal agent against most aerobic and anaerobic gram-positive cocci and bacilli. It has often been used effectively for MRSA, but it is expensive and nephrotoxic. There is no evidence that MRSA is any more virulent or invasive than susceptible strains. This is the drug of choice for treating MRSA. However, several MRSA have been isolated with plasmid-mediated resistance to vancomycin. This has prompted the use of others drugs such as quinupristin-dalfopristin, linezoid and daptomycin. These agents have good in-vitro activity against MRSA.
Since IV-line infections due to methicillin-resistant Staphylococcus aureus (MRSA) are infrequent, do not use vancomycin empirically for IV-line infections. If coagulase-negative staphylococci are recovered from the blood, do not use vancomycin empirically to treat these patients, since this is a low-virulence organism. Treatment of coagulase-negative, staphylococcal central-line infection requires removal of the line and not empiric vancomycin therapy.
Ciprofloxacin has Good activity against S. aureus including MRSA; Second-line agent used for osteomyelitis. Vancomycin is a glycopeptide antibiotic active against gram-positive bacteria. Used for severe life-threatening infections which other drugs have not treated successfully
including MRSA. It is also useful for Pseudomembranous colitis. Effective against MRSA are fluoroquinolones 2nd generation cephalosporins like ciprofloxacin, norfloxacin.
Methicillin-resistant S aureus (MRSA) are managed with intravenous vancomycin usually because these organisms are often hospital acquired. Community-acquired MRSA infections at more superficial, cutaneous sites may be susceptible to oral fluoroquinolones, clindamycin, or trimethoprim-sulfamethoxazole. Vancomycin resistance, GISA (glycopeptide intermediate resistance), is managed with antibiotics such as quinupristin-dalfopristin (Synercid), linezolid, or fluoroquinolones. For severe staphylococcal infections, a combination of a beta-lactam antibiotic and an aminoglycoside may be the initial treatment.
CONTROL OF OUTBREAK
In recent outbreak due to Methicillin-resistant S. aureus (MRSA), it has been necessary to close surgical wounds temporarily as part of the control measures. Mupirocin topical applications have proven useful for treating Methicillin-resistant S. aureus (MRSA) nasal discharge but recently Methicillin-resistant S. aureus (MRSA) have also acquired resistance against this agent.
TYPING OF ORGANISM
The main reason for typing of organism is to help clarify the possible routes of cross infection in an outbreak. Relevant accompanying epidemiological information is also important. A great majority of strains of S. aureus can be reproducibly phage typed using an international set of about 24 phages that are applied to each staphylococcal culture at a standardized dilution.
Epidemic strains of Methicillin-resistant S. aureus (MRSA) strains were often untypable with the standard set of phages but new experimental phages have proven useful. Examples of epidemic Methicillin-resistant S. aureus (MRSA) include: EMRSA-16 characteristic phage type 29/52/75/77/83A and resistant to methicillin, neomycin, ciprofloxacin, erythromycin often gentamycin and trimethoprim also; EMRSA-15 [phage weak 75]; and EMRSA-3 [phage 75/83A/932]. Non-typable strains can be investigated using pulse-gel electrophoresis of DNA digests from each strain.
ISOLATION PROCEDURES
Each hospital needs to have a policy of isolation for the isolation of patients with certain infections that may be transmitted to other patients or staff and if applicable the isolation of immunocompromised or other patients who are highly susceptible to infection. Skin lesions in patients with eczema or psoriasis are often heavily colonized of infected with S. aureus and these patients should be isolated as they spread large numbers of organisms into the air. Wound or skin sepsis due to Streptococcus pyogenes or to Methicillin-resistant S. aureus (MRSA) is also indications for isolation of patients.
PREVENTION
There is no effective vaccine against MRSA. Infection control procedures such as barrier precautions and disinfection of hands and fomites are important in the control of the infection. MRSA colonization/infection rates may be reduced by early eschar excision, wound closure, bacterial wound surveillance, and strict enforcement of infection control procedures.
Methicillin-resistant S aureus infection: Methicillin-resistant S aureus (MRSA) infection is a serious and increasingly common cause of nosocomial infection in patients with large burn wounds. Systemic vancomycin therapy and topical application of Mupirocin cream are indicated for burn wounds infected with MRSA. Hospital personnel who have been demonstrated to harbor MRSA should receive Mupirocin nasal ointment until surveillance culture results are negative.
Special situations warrant modification of this antibiotic treatment. For example, in patients who are hospitalized with suspected methicillin-resistant S aureus (MRSA), IV Vancomycin would be an appropriate regimen. Patients with prosthetic joints or intraarticular injected and subsequently infected joints are highly susceptible to MRSA and methicillin-resistant Staphylococcus epidermidis (MRSE), as well as Enterobacteriaceae and Pseudomonas. In this case, IV vancomycin and IV ciprofloxacin are appropriate choices.
Most cases of prosthetic valve endocarditis are caused by more resistant organisms (e.g., methicillin-resistant S aureus [MRSA], vancomycin-resistant enterococci [VRE], enteric gram-negative bacilli). In Prosthetic Valve Endocarditis caused by methicillin-resistant S aureus (MRSA), it should be treated with vancomycin at 30 mg/kg/d in 2 equally divided doses (usually, do not exceed 2 g unless serum levels are monitored) for 4-6 weeks. A peak vancomycin level of 30-45 mcg/mL should be attained 1 hour after completion of the intravenous infusion.
Vancomycin should be used initially for presumed line sepsis to cover methicillin-resistant S aureus (MRSA), endocarditis, and meningitis (in most areas due to highly resistant pneumococcus). In these situations, vancomycin should be continued until cultures exclude MRSA and demonstrate sensitivity to other agents.
Nonstreptococcal postinfectious glomerulonephritis can be caused by infection with methicillin-resistance staphylococcus aureus (MRSA) presenting as Nephritis of MRSA; this may have vasculitic lesions of the lower extremities. If methicillin-resistant Staphylococcus aureus (MRSA) is the inciting agent, then hypocomplementemia usually is not present, but plasma immunoglobulins, especially IgA, are elevated markedly. Nephritis associated with MRSA and chronic infections usually resolve after treatment of the infection
CONCLUSION
Methicillin-resistance staphylococcus aureus (MRSA) infection poses diagnostic and therapeutic intervention in infectious disease control. Aggressive methods can be adopted to manage outbreaks and prevent occurrence.
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