The spectrum and severity of these infections are similar to those caused by bacterial strains sensitive to antimicrobial drugs.
Good hand hygiene, appropriate institutional hygiene practices and avoidance of unneccessary courses of antimicrobials are the most important means in avoiding the spread of these microbes.
Asymptomatic carrier state does not limit normal life in home environment.
This article deals primarily with the control of MRSA infections. The same principles may be applied in the management of all infections caused by multi-drug resistant bacteria in hospitals and other health care institutions.
Definitions
MRSA
MRSA strains are S. aureus isolates, which are not susceptible to beta-lactamase resistant staphylococcal antibiotics (cloxacillin and dicloxacillin) or other beta-lactam antibiotics (such as cephalosporins and carbapenems). Of the new, so-called fifth-generation cephalosporins, ceftaroline and ceftobiprole are also to some extent effective against some MRSA strains.
In addition, MRSA strains are often multi-resistant in which case, for example, clindamycin, macrolides, aminoglycosides and fluoroquinolones have decreased effectiveness against them.
Community-associated MRSA strains have different drug sensitivity and genome than the typical hospital-associated MRSA strains. Community-associated strains are usually not multi-resistant.
This guideline applies in Scandinavia and in other areas where MRSA is not common.
ESBL
Extended-spectrum beta-lactamases (ESBLs) refer to beta-lactamases that are able to hydrolyze penicillins and cephalosporins.
Some ESBL strains are resistant also to other antimicrobial drugs, such as fluoroquinolones.
They are not able to break down antimicrobial agents of the carbapenem group.
Also newer combination drugs of cephalosporins and beta-lactamase inhibitors are effective against at least some ESBL strains.
Common ESBL producers include enterobacteria species normally found in the instestinal flora: Escherichia coli and Klebsiella spp. Sometimes ESBL production occurs in bacteria that cause intestinal infections, such as Salmonella spp.
CPE
Bacteria resistant to carbapenem-group antimicrobial drugs produce enzymes (carbapenemases) that break down carbapenems. Carbapenem-group drugs imipenem, meropenem, ertapenem and doripenem are effective against ESBL bacteria, but not against CPE bacteria.
Bacteria that may have carbapenemase-producing capacity include e.g. Klebsiella pneumoniae and Enterobacter spp.
Often carbapenemase-producing bacteria are resistant, in addition to carbapenems, also to almost all other antimicrobials, such as cephalosporins, penicillins and monobactams and also to the so-called beta-lactamase inhibitor combinations, such as amoxicillin-clavulanic acid and piperacillin-tazobactam.
Some CPE bacteria are susceptible to new combination drugs of beta-lactamase inhibitors and cephalosporins or carbapenems.
There are also CPE bacteria that are resistant to all antimicrobial drugs.
VRE
Enterococci are bacteria that belong to the intestinal microbial flora of healthy individuals. The most common enterococcus species include E. faecalis and E. faecium.
VRE refers to enterococci that have developed resistance to vancomycin (and often also to teicoplanin). VRE readily spreads in hospitals from one patient to another via the hands of the personnel or via the hospital environment. There are no antimicrobial drugs available for the eradication of carriage of VRE strains.
Epidemiology
The carrier prevalence of multidrug-resistant bacteria and the incidence of infections caused by them varies from country to country. Many of the involved persons are asymptomatic carriers. See local sources for more detailed information.
In South-Europe, France and the USA, 10-50% of infection-causing S. aureus strains are MRSA strains, whereas in the Nordic countries, Estonia and the Netherlands their share is below 1-5%.
In Finland, about 70% of MRSA-infections are detected in hospitals or other institutions. About half of the infections are aquired outside hospitals.
In some countries (e.g. the Nordic countries) the prevalence of MRSA is lower than in others (e.g. in the USA), at least partially due to moderate use of antimicrobials and successful preventive measures.
In screening, MRSA is found in people of all ages.
In a recent review, the cumulative global pooled prevalence of ESBL E. coli intestinal carriage in the community was found to be almost 17% (years 2003-18), with highest carriage rate in South-East Asia and lowest in Europe. An 8-fold increase was observed during the past two decades http://academic.oup.com/jac/article/76/1/22/5919862.
CPE and VRE bacteria are usually more rare than MRSA and EBSL bacteria.
In countries with low prevalence of multidrug-resistant bacteria, tourists returning from higher-prevalence areas may consitute a significant source of these bacteria, either as patients with an infection or as asymptomatic carriers. Tourists that have been treated in a hospital in high-prevalence areas are at a higher risk of carrying the bacteria.
Special events or circumstances, such as the COVID-19 pandemic and the war in Ukraine may have affected the prevalence of multidrug-resistant bacteria in different regions.
The spectrum and severity of infections caused by MRSA are similar to those caused by methicillin-susceptible S. aureus.
Community-associated MRSA infections are typically skin infections or urinary tract infections.
In intravenous drug users, bacteremic infections and skin infections are more frequent than in the normal population.
Hospital-aquired infections include surgical site and bone infections as well as bacteremic infections.
ESBL and CPE
These bacteria cause urinary tract infections and bacteremic infections.
CPE strains can cause problematic infections in ICU patients.
May also cause rarer infections in the gastrointestinal region, e.g. cholecystitis or appendicitis.
The virulence of ESBL and CPE bacteria does not differ from that of the ordinary E. coli or Klebsiella pneumoniae strains.
VRE
Enterococci belong to the normal bacterial flora of the human intestine and have a very low virulence. The most common infection caused by enterococci is urinary tract infection.
Enterococci cause severe infections typically in seriously ill intensive care patients and haematological patients with significantly reduced immunocompetence.
Prevention of multidrug-resistant bacteria
Even if the infections caused by multidrug-resistant bacteria (MRSA, ESBL, CPE and VRE) do not differ from infections caused by respective drug-sensitive bacteria, they are more difficult to treat because suitable antimicrobial drug alternatives are lacking.
It is important to prevent the emergence and spread of institutional epidemics by blocking the route of transmission. Hand hygiene, carrier isolation, rational antimicrobial use and good cleaning practices of the environment are the cornerstones of prevention. Each new infection caused by multidrug-resistant bacteria may mean significant cost for the hospital due to
isolation precautions
screening for colonisation
prolonged hospitalization of infected patients
increased work load of healthcare personnel.
Screening and diagnostics
MRSA
In order to prevent spread of MRSA, patients who are infected or colonised by MRSA should be identified as soon as possible after admission to the hospital.
A special MRSA culture is usually used to detect possible MRSA carrier state.
A nucleic acid detection test can by used for rapid detection or exclusion of MRSA when, for example, a patient with known exposure to MRSA is in the need of urgent surgery.
Bacterial cultures for MRSA screening and follow-up are performed on an individual basis. Local practices vary, but MRSA screening culture could be recommended to be taken from a patient admitted to hospital e.g. in the case that he/she
has earlier been found to be positive to MRSA (even if there had been negative MRSA cultures in between)
has received hospital treatment abroad during the past 12 months
has been treated in a hospital or other health care facility that is known to be endemic for MRSA
has during an earlier inpatient stay shared a room with a patient known to be positive to MRSA
has been treated on an inpatient ward during an MRSA outbreak on that ward.
It is recommendable to consult a specialist in infectious diseases or a medical microbiologist about the timing and technique of taking the MRSA cultures.
ESBL, CPE and VRE
ESBL is identified by screening culture. When investigating for possible colonisation, a stool specimen or a rectal smear is sent as a sample. The sample can also be obtained from an infection focus or from a site that was earlier colonised. In this case the sample is taken as any regular bacterial specimen. For urine ESBL culture, a urine specimen is delivered in a clean container.
CPE is included, together with ESBL, in the combined culture for multidrug-resistant Gram-negative rods.
VRE is detected by culture for vancomycin-resistant enterococci.
Ways of transmission
The most important way of transmission is through patients infected or colonised by multidrug-resistant bacteria.
In a hospital or other care institution, patient-to-patient transmission of MRSA strains may occur rapidly through direct contact, or often via the hands of the healthcare personnel.
Healthcare workers may become colonised with MRSA while taking care of MRSA-positive patients. This type of colonisation is a significant source of transmission only when the person has a skin disease or a defective skin area.
Among patients in hospitals or other care institutions, MRSA acquisition usually first leads to asymptomatic colonisation. The most common areas of colonisation are the nostrils, throat, perineum, groins, armpits and skin lesions (for example eczemas).
In outpatient care, MRSA skin infections are transmitted through near skin contact between individuals. The spread may also be indirect through touching materials or objects (towels, clothes, sports gear) that have been soiled by the discharge from a skin infection caused by MRSA.
ESBL, CPE and VRE often cause symptomless intestinal carriership.
Contact spread is a significant route of transmission in institutional epidemics caused by these bacteria.
If hand disinfection is not properly taken care of, the hands of the personnel act as vectors for the infectious agents between patients and from patients to the personnel.
These bacteria may also transmit via the hospital or institutional environment.
Transmission of these bacteria from, for example, the toilet of a patient room when the previous patient has been a carrier of these bacteria may be prevented also by thorough clean-up.
Prevention of transmission
Careful hand disinfection before and after all contact with patients is of most importance.
Instructions concerning MRSA are suitable for the prevention of infections caused by other multidrug-resistant bacteria as well (especially ESBL Klebsiella pneumoniae, CPE and VRE strains). There may be variation between organizations in the instructions concerning the treatment of ESBL E. coli carriers.
Consult local guidance and the relevant organisations (e.g. infection control units) or professionals (infection control nurse or physician) concerning detailed and case-specific instructions.
If possible, an MRSA patient should be isolated from other patients. Type of isolation may vary, depending on the situation. In hospital settings the patients should be placed in contact isolation. This is quite easy to accomplish if there are enough isolation rooms in the hospital, but in facilities for long-term care the problem is much more complicated.
When a patient on a ward is found to be MRSA-culture positive, it is advisable to screen at least his/her roommates for MRSA colonisation. If a second MRSA case is detected from the same hospital ward within a short time period, it is necessary to consider screening also other patients for MRSA colonisation.
In risk areas, like in intensive care and dialysis units, the screening of all other patients is justified already after one confirmed MRSA case.
Colonisation samples taken from the personnel are only seldom indicated. Follow the local instructions.
The infectious-disease specialist responsible for the regional control should always be contacted when investigation and treatment of the personnel is considered.
There should be plans prepared in advance on how to proceed if the samples would prove to be positive.
Samples from the personnel should be obtained in the beginning of the work shift because transient MRSA carrier status may occur during the working hours.
Careful privacy protection is necessary when samples taken from the personnel are handled.
The patient records of those patients who are known to have been colonised or infected by MRSA previously, should be labelled accordingly (in the section for risk data, if applicable). Contact isolation should be applied also during the next treatment episodes.
In case a patient is transferred to another healthcare facility, it is necessary to inform the receiving unit of his/her MRSA-status.
Treatment and follow-up
During hospitalization, patients who are infected or colonised by MRSA, VRE, ESBL-producing Klebsiella pneumoniae or CPE are treated in contact isolation.
MRSA acquisition often prolongs hospitalization. The patient should be discharged from the hospital as soon as it is possible without compromising patient care.
Treatment of MRSA infections and MRSA colonisation is performed in collaboration with a physician responsible for infection control or an infectious diseases specialist. The carrier state of resistant bacteria must not prevent the patient from receiving all treatment and care he/she needs without delay.
Colonisation
MRSA colonisation of an outpatient is usually not treated.
Among hospitalized patients treatment of asymptomatic MRSA colonisation may be indicated.
Treatment of MRSA colonisation should be considered before demanding surgery in order to reduce the risk of MRSA infection.
MRSA is often transmitted from a patient to health care workers involved in his/her treatment, but health care workers usually carry the bacteria only transiently. In cases with long-term MRSA-colonisation of a health care worker, eradication should be carefully considered as these workers may sometimes spread the disease later. The decision usually requires consultation of a specialist in infectious diseases with special expertise in this topic. The eradication may require testing of family members and sometimes even pets.
If colonisation is widespread or the patient has a severe skin disease, eradication of the bacterium will usually not be successful. Also foreign bodies (a urinary catheter, a tracheostomy tube, a nasogastric tube and different drainage tubes) may prevent successful eradication.
Systemic antimicrobial agents have rather poor effect on colonisation Antimicrobial Drugs for Treating Methicillin-Resistant Staphylococcus Aureus Colonization, because they are secreted to the mucosal surfaces only in a limited degree. Their usage should be considered if MRSA colonisation is very large-scale or affects areas of the body where local treatment cannot be administered. Systemic treatment of colonisation is reasonable only in exceptional cases.
Washing the patient with disinfectants (for example liquid soaps containing chlorhexidine) aims at diminishing the amount of bacteria on the skin and mucosal surfaces. There is no definite proof of its effect on treatment of colonisation.
The patient is considered cleared from colonisation if three consecutive MRSA-surveillance cultures taken at 1-week intervals are negative.
Relapses are, however, common especially if the patient has received antimicrobial treatment because of an infection. As relapses are possible even after several years, it is advisable to perform MRSA cultures from previously colonised patients every time they are readmitted to hospital.
The decision of whether MRSA carrier personnel should be removed from patient care is made by the physician responsible for infection control on individual basis. Staff who are solely nasal carriers are commonly allowed to continue work whilst being treated with mupirocin.
Symptomless carriers of ESBL, CPE or VRE bacteria need not be treated.
Infections
Apart from the choice of antimicrobial medication, MRSA infections are treated according to usual principles of care.
The first line treatment of community-associated soft tissue infections consists of incision and drainage of an abscess, as well as topical treatment rather than antimicrobial therapy.
In milder MRSA infections oral treatment may consist of, based on sensitivity testing, for example
intravenous or oral clindamycin 600 mg 3 times daily
Concerning the use of newer cephalosporins effective against MRSA, ceftaroline and ceftobiprole, in the treatment of complicated MRSA infections, it is recommended to consult an infectious disease specialist.
Some of the MRSA strains encountered in outpatient settings may show clindamycin resistance that is induced during the treatment.
If the treatment of an infection caused by ESBL or VRE requires use of an antimicrobial drug, choose it according to sensitivity testing.
National and international guidelines for prevention
Many countries have developed national guidelines for control of multidrug-resistant bacteria to be followed in the local circumstances.
Also regional or local guidance may be available. Consult relevant infection control nurses or physicians.
[Guideline on infection control of multi-resistant microbes]. Finnish Insitute for Health and Welfare (THL), Ohjaus 2/2020. Available in Finnish at http://urn.fi/URN:ISBN:978-952-343-463-9.