Epidemiology and Control of Epidemiology and Control of Methicillin-Resistant Methicillin-Resistant

Staphylococcus aureusStaphylococcus aureusin hospitalsin hospitals

Maria Kapi,MDMaria Kapi,MDRegistrar of Medical MicrobiologyRegistrar of Medical Microbiology

Laiko General Hospital of Athens, GreeceLaiko General Hospital of Athens, GreeceReadings: Readings: MRSAMRSA

What are MRSA?What are MRSA?

If we want to understand what are If we want to understand what are MRSA, we should first know:MRSA, we should first know:

1.1. What are Staphylococci?What are Staphylococci?

2.2. What is Staphylococcus aureus?What is Staphylococcus aureus?

What are MRSA?What are MRSA?

3. 3. What are penicillin and methicillin?What are penicillin and methicillin?4. What are PBPs?4. What are PBPs?

55. What are beta-lactams and beta-. What are beta-lactams and beta-lactames?lactames?

StaphylococciStaphylococci: : Gram positive cocci Gram positive cocci ( from Greek staphyle, means bunch ( from Greek staphyle, means bunch of grapes ) that occur singly and in of grapes ) that occur singly and in

pairs, short chains and irregular pairs, short chains and irregular grape-like clusters.grape-like clusters.

Staphylococcus aureus: Staphylococcus aureus: is the is the staphylococcus which has the ability to staphylococcus which has the ability to clot plasma or in other words, which is clot plasma or in other words, which is coagulase positive. More than 80% of coagulase positive. More than 80% of

Staphylococcous aureus Staphylococcous aureus strains produce strains produce beta-lactamases.beta-lactamases.

Penicillin: Penicillin: is the antibiotic agent that is the antibiotic agent that Alexander Fleming a Scottish physician Alexander Fleming a Scottish physician discovered in 1929. In 195 only 15% of discovered in 1929. In 195 only 15% of

S.aureus S.aureus was susceptible to penicillin. was susceptible to penicillin. Approximately 5% of Approximately 5% of S. S. aureus aureus today are sensitivetoday are sensitive to penicillin.to penicillin.

Methicillin: Methicillin: was with oxacillin the new line was with oxacillin the new line of penicillins in 1959, which became a of penicillins in 1959, which became a

new hope to the treatment of new hope to the treatment of St. aureus. St. aureus. In In 1961 the 1961 the St. aureus St. aureus became resistant to became resistant to

methicillin. Strains that aremethicillin. Strains that are

oxacillin and methicillin oxacillin and methicillin

resistant, historically termedresistant, historically termed

Methicillin-ResistantMethicillin-Resistant S.aureus S.aureus

(MRSA)(MRSA)

PBPsPBPs: are penicillin-binding proteins. : are penicillin-binding proteins. They are responsible for the final They are responsible for the final

stages of peptidoglycan synthesis of stages of peptidoglycan synthesis of the bacterial cell wall structure. the bacterial cell wall structure.

Inhibition of one or more of these Inhibition of one or more of these essential enzymes leads to bacterial essential enzymes leads to bacterial

lysis.lysis.

Beta lactams:Beta lactams: are the antibiotics that contain are the antibiotics that contain the beta lactam ring. These are : penicillins, the beta lactam ring. These are : penicillins, cephamycins, cephalosporins, carbapenems cephamycins, cephalosporins, carbapenems

monobactams. The ring structure is monobactams. The ring structure is common to all beta-lactams and must be common to all beta-lactams and must be

intact for antibacterial action. They are cellintact for antibacterial action. They are cell

wall synthesis inhibitors.wall synthesis inhibitors.

Beta lactamases: Beta lactamases: are enzymes that are enzymes that catalyse the hydrolysis of the beta-catalyse the hydrolysis of the beta-

lactam ring and inactivate these group lactam ring and inactivate these group of antibiotics. Genes encoding these of antibiotics. Genes encoding these

enzymes are widespread in the enzymes are widespread in the bacteria. bacteria.

What MRSA are doing?What MRSA are doing?

Methicillin Resistant Staphylococcus Methicillin Resistant Staphylococcus aureus, when its cell is exposed to aureus, when its cell is exposed to β-β-

lactam antibiotics, a supernumerary lactam antibiotics, a supernumerary β-β-llactam-resistant PBP (PBP2a), takes actam-resistant PBP (PBP2a), takes over the the biosynthetic functions of over the the biosynthetic functions of

the normal PBPs. This protein is the normal PBPs. This protein is responsible for the methicillin responsible for the methicillin

resistance.resistance.

Heteroresistance of MRSAHeteroresistance of MRSA

All the cell in the population may have All the cell in the population may have the genetic information for resistance , the genetic information for resistance , which is encoded by the which is encoded by the mecA gene.mecA gene.

Only a small number of cells can Only a small number of cells can actually express the resistant actually express the resistant

phenotype under in vitro testing phenotype under in vitro testing conditions. This phenomenon is termed conditions. This phenomenon is termed

heteroresistance.heteroresistance.

Why are MRSA important?Why are MRSA important?

1.1. Hospital –acquired infections. Hospital –acquired infections. MRSA MRSA are common nosocomial pathogens are common nosocomial pathogens around the world.around the world.

2.2. The treatment is very difficult. The treatment is very difficult. Vancomycin often is the only drug of Vancomycin often is the only drug of choice for severe infections.choice for severe infections.

Why are MRSA important?Why are MRSA important?

3.3. MRSA with reduced susceptibility to MRSA with reduced susceptibility to glycopeptides. glycopeptides. Since 1996 has been Since 1996 has been identified in Europe, Asia and United identified in Europe, Asia and United States. That increases the possibility States. That increases the possibility some strains became fully resistant to some strains became fully resistant to glycopeptidesglycopeptides. .

4.4. MRSA are easily transmissible MRSA are easily transmissible between patients.between patients.

MRSA in Europe.MRSA in Europe.

In England and Wales, fromIn England and Wales, fromJanuary to December 1999January to December 1999methicillin resistance was methicillin resistance was

37% of the 37% of the S.aureus S.aureus reports.reports.Except Scandinavia and Except Scandinavia and

Netherlands most countriesNetherlands most countrieshave high rates of MRSA.have high rates of MRSA.

MRSA in the United StatesMRSA in the United States

From January till December 1999, 52,3% From January till December 1999, 52,3% MRSA are associated with nosocomial MRSA are associated with nosocomial

infections in intensive care unit patients. infections in intensive care unit patients.

The increaseThe increase

in resistance in resistance

is 37% from is 37% from

1994-98.1994-98.

Epidemiology of MRSAEpidemiology of MRSA

Mode of Transmission. Mode of Transmission. Is transmitted Is transmitted by contact with a person who has by contact with a person who has

MRSA infection or is colonized with MRSA infection or is colonized with the organism.the organism.Hands of the health Hands of the health

care workers is the most common care workers is the most common mode of transmission from patient mode of transmission from patient

to patient.to patient.

Epidemiology of MRSAEpidemiology of MRSA

Reservoirs .Reservoirs .Colonized and infected Colonized and infected patients are the major reservoir of patients are the major reservoir of

MRSA. Although has been isolated MRSA. Although has been isolated from environmental surfaces, these from environmental surfaces, these

are not the most likely source of are not the most likely source of spread.spread.

Epidemiology of MRSA.Epidemiology of MRSA.

Risk factors. Risk factors. The factors that have been The factors that have been identified as increasing the risk of identified as increasing the risk of

MRSA infection are:MRSA infection are:

Increased length of hospital stayIncreased length of hospital stay Multiple hospitalizationsMultiple hospitalizations

WoundsWounds

Epidemiology of MRSA.Epidemiology of MRSA.

Risk factorsRisk factors

Invasive proceduresInvasive procedures Greater than 65 years oldGreater than 65 years old

Severe underlying disease.Severe underlying disease. Administration of broad-spectrum Administration of broad-spectrum

antibiotics.antibiotics.

Costs of MRSACosts of MRSA

Directly attributable costs: Directly attributable costs: “ “ hotel costs” of extended lengths of hotel costs” of extended lengths of

staystay the cost of diagnostic procedures, the cost of diagnostic procedures, morbidity and mortality that can morbidity and mortality that can

follow infectionfollow infection glycopeptides are more expensive glycopeptides are more expensive

than other antibiotics e.t.cthan other antibiotics e.t.c

Costs of MRSACosts of MRSA

Costs of control: Costs of control: costs of involvement of the infection costs of involvement of the infection

control team.control team. temporary closure of wards or temporary closure of wards or

theatres.theatres. re-deployment of staff.re-deployment of staff.

Control of MRSA in HospitalsControl of MRSA in Hospitals

General Principles: General Principles: Prevention of acquisition and spread Prevention of acquisition and spread

of infection by patients and staffof infection by patients and staff Priorities are high risk units, such as Priorities are high risk units, such as

intensive care units and patients who intensive care units and patients who are susceptible to infection.are susceptible to infection.

Control of MRSA in HospitalsControl of MRSA in Hospitals

Handwashing. Handwashing. Health care workers Health care workers should wash their hands before and should wash their hands before and after contact with all patients, even after contact with all patients, even when gloves are worn. A written when gloves are worn. A written protocol detailing proper hand wash protocol detailing proper hand wash technique should be available for technique should be available for reference.reference.

Control of MRSA in HospitalsControl of MRSA in Hospitals

GlovesGloves should be worn when in contact should be worn when in contact with any body substance. Gloves with any body substance. Gloves should be changed and hands washed should be changed and hands washed immediately after contact with each immediately after contact with each resident.resident.

Appropriate use of antimicrobials.Appropriate use of antimicrobials. Monitoring and auditing of drug use.Monitoring and auditing of drug use.

Control of MRSA in HospitalsControl of MRSA in Hospitals

Isolation Isolation is necessary for infected is necessary for infected patients and possible carriers in a patients and possible carriers in a single room or preferably in an single room or preferably in an isolation unit with designated staff. isolation unit with designated staff. Isolation reduce staphylococcal cross-Isolation reduce staphylococcal cross-infection.infection.

Control of MRSA in HospitalsControl of MRSA in Hospitals

Ward Closure Ward Closure should be considered should be considered when new patients become infected when new patients become infected with MRSA. The presence of strains of with MRSA. The presence of strains of MRSA causing invasive infection is MRSA causing invasive infection is another indication.another indication.

Screening of patients for MRSA Screening of patients for MRSA at the at the nose, throat and perineum.nose, throat and perineum.

Control of MRSA in HospitalsControl of MRSA in Hospitals

Carriage of MRSA by health care Carriage of MRSA by health care workers. workers. During outbreaks staff should During outbreaks staff should be reminded of the handwashing and be reminded of the handwashing and transient carriage of MRSA. Staff with transient carriage of MRSA. Staff with infected or colonized lesions should infected or colonized lesions should not be at work especially in critical not be at work especially in critical areas, as intensive care units, areas, as intensive care units, cardiothoracic words e.t.c.cardiothoracic words e.t.c.

Control of MRSA in HospitalsControl of MRSA in Hospitals Treatment of carriers.Treatment of carriers. Nasal carriage is Nasal carriage is

treated topical with mupirocin.treated topical with mupirocin. Systemic treatment of infectionsSystemic treatment of infections The The

glycopeptide antibiotics are currently glycopeptide antibiotics are currently the agents of choice for treatment.the agents of choice for treatment.

Microbiological characterization of Microbiological characterization of MRSA.MRSA.

Antimicrobial resistance: is a Antimicrobial resistance: is a major threat to public health.major threat to public health.

Bacterial resistance to multiple Bacterial resistance to multiple antibiotics characterises the present antibiotics characterises the present decade. Finding organisms resistant to decade. Finding organisms resistant to over 10 different antibiotics is not over 10 different antibiotics is not unusual.unusual. Globally we need to look at Globally we need to look at how antibiotics are used andhow antibiotics are used and

reduce their inappropriate use.reduce their inappropriate use.