California
Association
for
Medical Laboratory Technology
Distance Learning Program
| THE
SUPER BUGS ©
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THE SUPER
BUGS—MRSA, VRE, VISA, VRSA
(Methicillin resistant Staphylococcus aureus, Vancomycin resistant
Enterococcus,
Vancomycin intermediate Staphylococcus aureus, Vancomycin resistant
Staphylococcus aureus)
At the end of this course the participant will be able to:
- Summarize the evolution of resistance in Staphylococcus aureus.
- Define the “super bugs” (resistant gram positive strains).
- Summarize the ways antibiotics work.
- Outline various methods of resistance found in microorganisms.
- Contrast CA (community acquired)-MRSA (methicillin resistant Staphylococcus aureus) to HA (hospital acquired)-MRSA.
- Discuss solutions to “selective resistance” through prevention and control.
- Discuss the need for alternative therapies.
- Describe the accepted methods of detection.
INTRODUCTION
The progress of antibiotic resistant strains of Staphylococcus aureus
from the strictly nosocomial (hospital-acquired) into the community has taken
an insidious route. The first penicillin-resistant strains were encountered
in the 1940s, a few years after Alexander Fleming’s renowned discovery
of the antibiotic. Following World War II, a predominance of these resistant
“bugs” spread internationally. Thus began a relentless parade of
antibiotic resistance that led to the dilemma we presently face with resistance
to vancomycin.
Past reports showed there were certain similarities between penicillin-resistant S. aureus and the methicillin-resistant S. aureus strains that appeared in the 1960s. In both situations, nosocomial colonization of the healthcare staff led to transmission of infection among hospitalized patients, and to their direct or indirect contacts in the community. Years elapsed before either penicillin-resistant or methicillin-resistant organisms appeared from a community reservoir without hospital associated exposure or other risk factors. These community acquired organisms were not resistant to other antibiotics, whereas the nosocomial cases were multiply resistant. As the incidence of MRSA began to rise, the differences between hospital-acquired MRSA (HA-MRSA) and community-acquired MRSA (CA-MRSA) became more distinct. The risk factors for infection also changed dramatically.
By 1980, high-risk groups, particularly IV drug abusers, patients infected with HIV, and those with other immunosuppressive diseases, required antibiotic therapy. Patients who were previously treated with antibiotics and those who were non-compliant added to the epidemiologic burden.
Unlike penicillin or methicillin resistance, vancomycin resistance took nearly forty years to appear after its introduction in 1956. A member of the Enterococcus spp. known as VRE (vancomycin resistant Enterococcus), was the first organism to acquire resistance to vancomycin and the one that brought pandemonium to a mid-western medical center before stringent infection control measures were enforced. (1, 6) The incessant march of antibiotic resistance requires the establishment of programs to prevent the spread of resistant microorganisms and control the use of antimicrobial drugs in health care settings.
NOTE: This course will cover only resistant gram positive organisms: MRSA, VISA, VRSA, and VRE
DISCUSSION
Less than a year after its discovery in England in 1959, methicillin, the replacement
for penicillin, led to the development of the first “super bug,”
MRSA. Two years later resistance followed in all beta-lactam replacements—oxacillin,
nafcillin and the cephalosporins—contributing to a susceptibility pattern
of multiple-resistance. For decades selective resistance resulting from excessive
antibiotic use has pressured researchers to design more complex drugs in an
attempt to trick these bacteria into submission. (1)
With what seemed remarkable déjà vu to the 1950’s penicillin-resistance epidemic in hospital nurseries, two outbreaks of MRSA that occurred in Los Angeles in 2001 implicated breast milk. Presenting at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Dr. Dawn Terashita of the Los Angeles County Health Department described cases from outbreaks in two separate neonatal intensive care units. Mothers who were treated for mastitis with dicloxacillin proved to be carriers of MRSA in their breast milk. Confirmation was supported by microbiology culture. One infant died, another developed septicemia, and all infants, including quadruplets, were colonized with the organism. (2)
In 1996 the first dreaded case of decreased susceptibility to the “magic bullet” appeared—vancomycin-intermediate susceptible S. aureus (VISA). Prevention and control guidelines were established by the Centers for Disease Control and Prevention (CDC) to deter empiric treatment with the drug. But after six years, the inevitable SUPER bug evolved—VRSA, a strain that had become completely resistant to vancomycin. Distinguishing between VISA and VRSA requires observation of the difference in their MIC (minimal inhibitory concentration, the serum level concentration required for an antibiotic to inhibit a microorganism). That level for VISA is ≥ 8 mg/ml (8-16 mg/ml) and for VRSA is ≥ 32 mg/ml. These values are the laboratory breakpoints to guide therapy as determined by the Clinical Laboratory Standards Institute (CLSI/NCCLS). (3)
The first case of VRSA in the U.S. was isolated in 2001 from a catheter exit site in a 40-year old diabetic patient from Michigan. He also suffered from peripheral vascular disease and chronic renal disease that required dialysis treatment. After undergoing the amputation of an infected toe, he developed bacteremia with a MRSA when his dialysis graft site became infected. (The graft site provided access for the dialysis machine.) His previous antibiotic therapy had initially included vancomycin and rifampin. He also had foot ulcers infected with VRE. The VRSA super bug that devastated the Michigan patient was remarkable in its ability to combine both the mecA gene from MRSA and the vanA gene from VRE that were identified by genetic sequencing. Fortunately, this super bug was susceptible to other available antibiotics, one of which was trimethoprim/sulfa given intravenously. In vitro tests showed the bug was also susceptible to the FDA-approved antibiotics, linezolid and quinuprisitin-dalfopristin, as well as minocycline and an investigational drug, daptomycin.(4)
Not only had previous cases of multiple-resistance appeared in high risk patients, but the cases had also been hospital-acquired. Therefore, infectious disease specialists were alarmed to hear a case presentation by University of Texas researchers at the Infectious Disease Society of America (IDSA) meeting in San Diego, CA in 2003. A previously healthy child taken to the Hermann Children’s Hospital in Houston had become critically ill due to the formation of a blood clot in his leg that resulted from infection with a drug-resistant Staphylococcus aureus. This case involved a community-acquired organism, as opposed to a hospital-acquired organism, with an MIC equal to 1024 µg/ml, an unheard of MIC elevation by a bacterium once easily eradicated with penicillin! (5)
MECHANISMS OF RESISTANCE:
Antibiotic resistance of microorganisms can be natural or acquired. Some species,
such as Pseudomonas aeruginosa, show a natural high resistance to a
number of antibiotics whereas others, such as group A streptococci,
are normally susceptible. Acquired resistance evolves through genetic alterations
in the microorganism's own genome or by transfer of resistance genes located
on various types of mobile DNA elements.
In order to understand antibiotic resistance it is necessary to know the various ways antibiotics work, as follows:
- bacterial cell wall inhibitors—vancomycin and beta-lactams (penicillin, cephalosporin, etc.)
- inhibition of enzymes involved in replication of DNA—quinolones
- inhibition of transcription by binding to bacterial RNA-polymerase—rifampin
- inhibition of proteins synthesis by interfering with 70S ribosomal function—macrolides, tetracycline, aminoglycosides
- inhibition of biosynthesis of tetrahydrofolic acid thus interfering with DNA synthesis—sulfonamides and trimethoprim
- inhibition of the initiation step of protein synthesis—oxazolidinones,
discovered in 1999, to replace vancomycin
For each class of antibiotics there are a number of microbial mechanisms that can cause resistance. The main mechanisms include:
- decreased uptake of the drug (modified cell membrane which reduces permeability)
- increased export of the drug (increased activity of efflux pumps)
- inactivation or modification of the drug target in the microorganism (mutations in ribosomal proteins, penicillin binding proteins, mutation of ribosomal RNA, etc.)
- introduction of a new drug resistant target (i.e., mecA gene in methicillin resistance) or bypassing the targeted metabolic reaction (i.e., a novel dihydrofolate reductase in trimethoprim resistance)
- hydrolysis of the antibiotic (beta-lactamase)
- modification of the antibiotic (aminoglycoside modifying enzymes)
- Penicillin (beta-lactam antibiotics) resistance is due to beta-lactamase (penicillinase) which breaks down the beta-lactam antibiotics. Resistance most often is acquired by horizontal transfer of a plasmid containing the bla gene which codes for production of beta-lactamase, or less commonly by constitutive mutations in the genome which cause increased production of the beta-lactamase enzyme.
- Methicillin resistance is due to the mecA gene which encodes an altered penicillin binding protein (PBP2a) with low affinity for beta-lactam antibiotics.
- Vancomycin resistance is due to vanA and vanB genes which code for an alteration in the precursor compound to the peptidoglycan bacterial cell wall, decreasing the ability of vancomycin to attach to its target in the normal peptidoglycan precursor compound.
MRSA
Most MRSA resistance is determined by the mecA gene, although some
methicillin resistance in Staphylococcus aureus can be explained by
strains that have hyper beta-lactamase production or by non mecA mediated
alteration of penicillin-binding proteins (PBPs). The mecA gene is
chromosomally encoded, in contrast to the plasmid encoded penicillinases. MecA
confers resistance not only to beta-lactams, but also to antibiotics such as
aminoglycosides.
MecA is a large element called a resistance island that is only rarely transferred horizontally from one organism to another because of its size and complexity. The rarity of transfer accounts for the small number of ancestral strains which resulted in all clinical isolates worldwide. Ribotyping and cluster analysis have been employed to identify five distinct clones of MRSA. This is a relatively small number when compared to the enormous number of methicillin-sensitive clones.
Until recently strains of MRSA were found primarily in hospitals and long term care facilities. In 1999 MRSA was isolated from children in the community (i.e., not hospital associated). The thinking is that the community-acquired strains may have evolved during a rare transfer from a nosocomial donor organism to a susceptible community recipient. (1) The CA-MRSA strains differ from HA-MRSA. (Table 1) HA-MRSA has other resistance genes that make it multiply-resistant, unlike the more sensitive patterns seen in CA-MRSA, which has acquired only one resistance gene, making it more similar to a wild strain.
Presentations at the 41st ICAAC in 2001 by researchers from universities of Nebraska, Minnesota, and San Francisco indicated that the CA-MRSA strains were capable of producing superantigens. Unlike the HA-MRSA strains, the superantigens have been described as having toxin producing virulence factors in both staphylococci and streptococci with the potential to cause toxic shock syndrome. The HA-MRSA strains, although multiply-resistant to antibiotics, have not been associated with toxic shock.
VRE
Like the staphylococci, enterococci are capable of both induced
and acquired types of resistance: inducible beta-lactamases transferred horizontally
via plasmids, and chromosomal resistance via altered penicillin binding protein
(PBP) sites on the organism’s cell wall. VREs were first reported in 1986
after extensive treatment with vancomycin was used in cases of antibiotic-associated
diarrhea and pseudomembranous colitis caused by a multiply-resistant
organism, Clostridium difficle. The highly complex vanA and
vanB operons were found to contain both regulating and essential genes
required for the expression of resistance. Evidence for status as acquired rather
than intrinsic came from examination of the guanine-cytosine (G-C) content of
the vanB operon, which contained 50% G-C rather than the usual 35 %
to 40% present in most enterococcal genes.
Both vanA and vanB resistance involve substitution of the D-lactate for the D-alanine moiety at the terminal of pentapeptide precursors present at certain PBP sites during the bacterial cell wall synthesis.
Colonization of the gastrointestinal (GI) tract with VRE occurred when high levels of vancomycin were administered, but not absorbed by the intestinal tract. Similarly, in the European outbreak of VRE, animals that were used for food had ingested vancomycin as a growth promoter, a situation that led to colonization of their GI tracts.
Treatment with cephalosporins and other beta-lactams that inhibit the growth of normal gut bacteria can increase colonization of the GI tract by VRE. However, when treatment was administered using the antibiotics directed against anaerobic bacteria, no synergistic effect was observed. (6)
VISA
Although the mechanism of resistance for this super bug is not completely understood,
a probable explanation exists. In 1999 strains of intermediate-resistant Staphylococcus
aureus, which had MICs in the range of 8-16 µg/ml were shown not
to contain the vanA, B, or C genes of VRE. However,
cell walls of these strains had absorbed vancomycin in varying amounts which
created a thicker than usual cell wall layer. These strains were found to have
reduced susceptibility to vancomycin. (7)
In 2000 at the 40th meeting of the Infectious Disease Society of America, Barbara Murray, MD of the University of Texas School of Medicine, Houston, Texas, explored problems with vancomycin and other glycopeptides. She emphasized the greater potential for transmission of infection found in VISA because of its plasmid-mediated (rather than chromosomal-mediated) resistance. One strain can evolve to become a variety of strains with different sensitivity patterns because of the differences in cell wall thickening that prevents vancomycin absorption at the binding sites: hence, the range of intermediate resistance from 8-16 µg/ml.
VRSA
In the laboratory, conjugative transfer was accomplished by taking the vanA
gene from a VRE strain of Enterococcus faecalis and introducing it
into a strain of Staphylococcus aureus. The work was done by W.C. Noble
and co-workers, who published their findings in Microbiology Letters, 1992.
Although the assumption was made in 2002 (after the first U.S. case of VRSA arose in the Michigan patient) that conjugative transfer of the vanA gene must have come from the patient’s own VRE, the second case gave researchers pause. The organism in that case, from a patient at the Pennsylvania State Hershey Medical Center, proved to carry a vanA plasmid which was not only unlike that of his VRE, but also unlike the one isolated from the Michigan patient. The first case had an MIC = 1024 µg/ml and the second, MIC = 32 µg/ml. (8)
In a 2004 article published by workers in both New York and Atlanta, the two major mechanisms of resistance, the mecA gene and the vanA plasmid were elegantly presented. A transconjugant named COLVA (from the MRSA strain named COL and VA from the vanA strain of VRE) showed homogeneous resistance to both oxacillin and vancomycin. When grown in vancomycin-rich medium COLVA was able to make an abnormal peptidoglycan. Pentapeptides had been replaced by tetrapeptides and the peptidoglycan contained more than 22 muropeptide species with a deficit or absence of branches. When the researchers inactivated the mecA gene, loss of beta-lactam resistance occurred, but there was no effect on vancomycin resistance. Thus, it was concluded that in VRSA where both mecA and vanA resistance mechanisms exist, different sets of enzymes are employed in the formation of the organism’s cell walls. (9)
PREVENTION AND CONTROL:
As an attempt to regulate hospital procedures, CDC added all new cases of MRSA
and VRE to the list of conditions for which universal precautions are recommended.
(The term universal precautions first appeared during the 1980s HIV epidemic.)
These precautions require specific steps to protect both hospital personnel
and patients from transmission of infectious agents.
Further guidelines issued by CDC outlined the following risk factors for infections with super bugs:
- Patient transfer between institutions, especially nursing homes
- Severity of illness, i.e. high-risk patients (HIV, immunocompromised patients, diabetics and the elderly)
- Presence of foreign device or implant (catheters, prostheses etc.)
- Days of hospitalization (recommended limit <72 hours)
- Use of multiple antibiotics
An example of good hospital infection control practice, chosen for its thoroughness and proven track record, was presented as a special issue in the 2001 CDC section report of “Emerging Infectious Diseases.” (10) The article was written by Robert A. Weinstein, M.D., Director of Infectious Diseases at Cook County Hospital in Chicago, Illinois, who is a specialist in the epidemiology and control of antimicrobial resistance and infections in intensive care units. The report described specific interventions, along with supporting statistics, for the effective control of nosocomial infections.
Guidelines with detailed instructions included the following:
- hand hygiene using alcohol-based hand rubs
- universal gloving in response to “colonization pressure” (increase in the number of colonized patients, which is directly proportional to the likelihood of the cross-transmission of infection)
- rotating or “cycling” the use of antibiotics or combination therapy, a technique shown to reduce patient colonization with VRE and with MRSA.
Alternative antibiotic therapies were shown to be decreasingly effective when the National Nosocomial Infection Surveillance (NNIS) System compiled the data of hospitalized patients for 1992-2003. The rise in cases of MRSA in U.S. hospital intensive care units had reached an all-time high of 57% when the report was published, and the number of non-ICU patients reached 49%. On the other hand, the rate for VRE, the resistant strains of Enterococcus spp., though still a serious threat, had declined from 40% in 1999 to 20% in 2000 after infection control intervention prevailed. To that point, the two glycopeptides, vancomycin and teichoplanin, had been the drugs of choice for treating and preventing the spread of MRSA. When reports showed an increasing incidence of VISA, another update by CDC was needed to direct infection control guidelines toward preventing an impending crisis.
In spite of the successes noted in those who followed the Cook County guidelines, many institutions still struggled with ongoing and intractable transmission of infection. The predominant message was not new, and applied to the community as well as to hospital workers—improved hand washing techniques in all medical personnel seemed a simple and effective deterrent. A newly developed alcohol gel, less damaging to skin and dispensed by automated hand sanitizers or impregnated in disposable towelettes, has been found to exceed the antiseptic effect of soap solutions in preventing transfer of pathogenic organisms among patients. The sanitizers or alcohol gel-impregnated disposable towels were placed at convenient locations in hospitals and clinics. Unfortunately, surveys showed that compliance, although better than with antibacterial soaps, reached just 50% among physicians, nurses, and other healthcare workers. (4)
According to studies presented at the 2003 San Diego meeting of the IDSA, infections with resistant strains of S. aureus were presumed to have migrated from hospitals into the community a few years ago. Not surprisingly, they have been found in areas where children are in close contact, on sports teams, and in day care centers. Tracking transmission of a nosocomial infection in the hospital can be difficult, but gathering and screening data from the community presents a daunting task. Confounding factors (variables that contribute to complexity of the study) include previous antibiotic use, immune status, number of exposures to infected people, and exposure to contaminated materials in the environment. (5)
DIAGNOSTIC LABORATORY METHODS:
MRSA —Methods of Detection (3, 11)
Mechanisms of resistance
MRSA is defined by its ability to acquire the mecA gene that codes
for PBP2a, a penicillin-binding protein with decreased affinity for beta-lactam
antibiotics. Other factors such as excess beta-lactamase production or changes
in PBPs may cause phenotypic expression of resistance (to methicillin, oxacillin,
etc.) in strains of S. aureus that lack the mecA gene. But
because the latter mechanisms rarely occur, CLSI/NCCLS 2005 (3) recommends results
for MRSA isolates should be reported as follows:
- when mecA is positive; PBP2a produced, oxacillin is resistant, MIC ≥ 4 µg/ml
- when mecA is negative; PBP2a not produced, oxacillin is susceptible, MIC ≤ 2 µg/ml
- when mecA is negative; PBP2a not produced, but MIC ≥ 4 µg/ml, oxacillin is considered resistant and should be reported as such.
Phenotypic detection
- Oxacillin agar screen
Medium: Brain heart infusion agar (BHIA) or Mueller-Hinton agar (MHA) with 4% NaCl and 6 µg/ml oxacillin added
Inoculum: Direct colony suspension to obtain a 0.5 McFarland turbidity
Use a 1 µl loop or a swab dipped in the suspension
Apply to agar making a 10-15 mm diameter spot
Incubation: 30°-35° C for ≥ 24 hours in ambient air
Interpretation: Growth of > 1 colony indicates resistance
Quality Control: Staphylococcus aureus ATCC 29213—Susceptible
Staphylococcus aureus ATCC 43300—Resistant
- Disk diffusion: media, inoculum and incubation as for oxacillin screen (above);
interpretation and reporting per CLSI/NCCLS, 15th supplement
- Broth dilution: E test® (AB Biodisk, North America, Inc., Piscataway,
New Jersey),
MIC by a gradient elution method
- Automated systems
Vitek® (bioMerieux, Hazelwood, MO)
Vitek 2® (bioMerieux)
MicroScan® (Dade Behring, Deerfield, IL)
Sensititre® (Trek, Westlake, OH)
Other: Conventional panels, Rapid panels
MRSA Screen (Denka Sieken, Tokyo, Japan) latex agglutination for detection of PBP2a
Velogene™ (Rapid MRSA Assay) (REMEL, Lenexa, KS)
PCR (in-house assays, available from Roche Molecular Biochemicals, Indianapolis, IN)
- Interpretation and Reporting: Detailed instructions for standardized testing, interpretation and reporting can be found in CLSI/NCCLS 6th Edition (3)
- Although molecular detection of the mecA gene is the most reliable method of identifying MRSA, phenotypic detection methods are used by most laboratories, which usually have several methods available capable of detecting ≥ 90% of mecA-positive strains and 86% of mecA-negative strains.
- Because specimens are often obtained from non-sterile sites, the presence of contamination by coagulase-negative staphylococci, which is commonly multiply-resistant, must be ruled out.
- Epidemiologic and molecular testing can be done at state reference laboratories or at CDC laboratories. (11)
VRE—Methods of Detection (3)
Mechanisms of resistance
Encoding for acquired resistance are the vanA and vanB genes,
which are generally found in Enterococcus faecium and Enterococcus
faecalis. Beta lacatamase production has also been implicated
as a mechanism. Intrinsic resistance or intermediate-level resistance is encoded
by vanC and found
in E. gallinarium, E. casseliflavus or E. flavescens.
For purposes of infection control data collection, organisms that display the
intermediate level of resistance (MIC 8-16 µg/ml) are not included.
MIC for acquired resistance ≥ 32 µg/ml
MIC for intrinsic resistance 8-16 µg/ml
Phenotypic detection
- Vancomycin agar screen
Medium: Brain heart infusion agar (BHIA) with 6 µg/ml of vancomycin added
Inoculum: 1-10 µl of a 0.5 McFarland suspension spotted on agar surface
Incubation: 30°-35°C for ≥ 24 hours in ambient air
Interpretation: Growth of > 1 colony = presumptive resistance
Quality Control: Enterococcus faecalis ATCC 29212—Susceptible
Enterococcus faecalis ATCC 51299—Resistant - MIC tests should be performed by
Automated systems, followed by broth dilution or E Test® to determine high-level resistance: ≥ 32 µg/ml
Mechanisms of resistance
Traditional biochemical and gene sequence analysis are performed by CDC to identify VRSA. This super bug not only has the mecA gene that encodes oxacillin resistance in S. aureus, but also the vanA gene that encodes vancomycin resistance.
MICs define resistance as follows:
(VISA) = 8-16 µg/ml
(VRSA) ≥ 32 µg/ml
Phenotypic Methods of Detection (4)
- Vancomycin agar screen
Medium: BHIA or MHA (with 4% NaCl); 6 µg/ml vancomycin added
Inoculum: 1-10 µl of 0.5 McFarland suspension spotted on agar
Incubation: 30°-35°C ≥ 24 hours in ambient air
Interpretation: Growth of > 1 colony = presumptive resistance
- Broth microdilution, agar dilution, or agar gradient must be performed to confirm intermediate or resistant strains
Reporting: Confirmed or presumptive vancomycin resistance should be reported
to:
Division of Healthcare Quality Promotion, National Center for Infectious Diseases,
CDC, telephone 800-893-0485
*Additional guidelines for prevention of transmission are available at:
www.cdc.gov/ncidod/hip/vanco/vanco.htm
Epidemiologic Testing (12) (See Table 1.)
Table 1. (ICAAC 2004)
| Comparison of Hospital-Associated MRSA (HA-MRSA) and Community-Acquired MRSA (CA-MRSA) | ||
| Property | HA-MRSA | CA-MRSA |
| MecA | Type II | Type IV |
| PFGE* type | US 100 | US 300 |
| Toxins | Few | More |
| PVL# | Rare | Common |
| Antibiotic Resistance | Multiply Resistant | Beta-lactam resistant only |
Methods to identify strain relatedness:
Pulsed-field gel electrophoresis (PFGE) for strain type
Multilocus sequence typing
Staphylococcal Cassette Chromosome mec (SSCmec, formerly mecA)—testing of 5 types (I-V)
Virulence factors—toxin studies include Panton-Valentine leukocidin (PVL), enterotoxin H and multiple superantigens
CONCLUSION
The rising incidence of resistant bugs appearing in the community set off an
alarm in the medical world. Before sequencing and epidemiologic techniques,
such as the identification of toxins and virulence factors, were applied to
differentiate strain types, the assumption was that community-acquired MRSA
(CA-MRSA) evolved directly from hospital-acquired MRSA (HA-MRSA). But an overall
sensitive antibiotic pattern was seen in the community strain(s) unlike that
seen in the highly-resistant nosocomial strains. The resistance mechanisms differ
as well. Penicillin resistance is readily transferred horizontally via plasmid-coding;
whereas, MRSA is chromosomally encoded through the mecA gene, which
is rarely transferable horizontally. When definitive techniques were applied
to CA-MRSA, presence of the mecA gene and its types (I-IV), PFGE type,
presence of toxins and virulence factors determined that variations in strain-type
were indeed remarkably different from HA-MRSA. The “community bugs”
were decidedly more deadly! Further concern mounted when the rising incidence
of community-acquired pneumonias was added to soft tissue infections. These
pneumonias, caused by both MRSA and methicillin-sensitive (MSSA), can result
in severe disease leading to life-threatening necrotizing pneumonia. (1, 12)
How do we protect the community from these super bugs? Increased awareness and monitoring are paramount in crowded areas where skin and soft tissue infection can easily spread—daycare centers, sports teams, prisons, military barracks, and nursing homes. On the preventive side, observing CDC guidelines, confirming the diagnosis with culture of infective material, notifying the public health department, keeping wounds covered, educating healthcare providers, and adhering to universal precautions have all become essential steps. Successful treatment of soft tissue infection has been accomplished with clindamycin, trimethoprim-sulfamethoxazole or doxycycline. For cases of severe disease, vancomycin plus nafcillin (with or without gentamicin) or linezolid can be used. Focusing community awareness on prevention and control is the only way to offset serious outbreaks and/or to implement improved patient care and recovery. (12)
REFERENCES
- Chambers HF. The changing epidemiology of Staphylococcus aureus? Emerging Infectious Diseases. 2001;7,2:178-182
- Program and abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; October 30-November 2, 2004; Washington, DC
- Clinical Laboratory Standards Institute (CLSI/NCCLS), Approved Standard 2005 15th informational supplement, CLSI/NCCLS document M07-6, Table 2C:110-115 www.nccls.org
- Centers for Disease Control and Prevention, Staphylococcus aureus resistant to vancomycin—United States 2002. MMWR 2002;51(26):565-567 www.cdc.gov/mmwr
- Presentation by University of Texas at the meeting of Infectious Disease Society of America (IDSA), San Diego, CA 2003
- Rice LB. Emergence of vancomycin resistant enterococci. Emerging Infectious Diseases. 2001;7(2), ”2001 Centers for Disease Control and Prevention (CDC)
- Smith TL, Pearson ML, Wilcox KR, et al. Emergence of vancomycin resistance in Staphylococcus aureus. NEJM 1999;340:493-501
- Whitener CJ, Park SY, Browne FA, et al. Vancomycin-resistant Staphylococcus aureus in the absence of vancomycin exposure. Clinical Infectious Diseases. 2004;38(8):1049- 1055
- Severin A, Keiko T, Tenover F, et al. High level oxacillin and vancomycin resistance and altered cell wall composition in Staphylococcus aureus carrying the Staphylococcal mecA and the enterococcal vanA gene complex. Journal of Biological Chemistry. 2004;279(5):3398-3407
- Weinstein RA. Controlling antimicrobial resistance in hospitals: infection control and use of antibiotics. Special Issue, Emerging Infectious Diseases 2001;7(2)
- Hall G. MRSA: Detection, epidemiology and infection control. In: Microbiology Frontline‘, Volume 3, Number 1, May 2003 www.microbiologyfrontline.com
- Bartlett JG. Update on community-acquired MRSA, presentation at the 44th Interscience Conference on Antimicrobial Agents in Chemotherapy (ICAAC), November 2, 2004, Washington, DC
Review Questions Course #: DL-964 - Select the one best answer
for each question
Submit answers for CE credit - On-line
REGISTRATION, PAYMENT and QUIZ
- Penicillin resistance in Staphylococcus aureus spread
a. across the world in the 1940s
b. during a 1980’s epidemic among drug abusers
c. 10 years after Fleming’s discovery of penicillin
d. among hospital patients only - Groups with high risk for infection with resistant organisms include all
of the following except
a. HIV infected patients
b. previous treatment with antibiotics
c. patients compliant with antibiotic therapy
d. patients hospitalized for over 3 days - Outbreaks of VRE
a. were common in day-care centers
b. had a similar antibiotic resistance pattern to VISA
c. appeared in strains of Enterococcus spp. about 1996
d. first appeared in the community - The MIC level for VISA set by CLSI/NCCLS is
a. 8-16 µg/ml
b. <32 µg/ml
c. 4 µg/ml
d. 2-8 µg/ml - Beta-lactam antibiotics and vancomycin work in bacteria by
a. interfering with 70S ribosome function
b. inhibiting cell wall formation
c. inhibiting biosynthesis of tetrahydrofolic acid
d. binding to RNA polymerase - Bacterial resistance to beta-lactams can be due to
a. decreased uptake
b. increased export
c. bypassing the metabolic reaction
d. hydrolysis of the antibiotic - The mechanism of resistance in MRSA does not include
a. presence of the mecA gene types II and IV
b. beta-lactamase production
c. plasmid transfer of the mecA gene
d. altered penicillin binding protein (PBP) - The complex resistance attributed to VRSA can be explained by the
a. interaction between the mecA and vanA genes
b. cell wall absorption of vancomycin and subsequent thickening
c. beta-lactamase action on vancomycin
d. plasmid-mediated resistance of mecA - CDC’s risk factors for infection with super bugs include all except:
a. a TB patient previously treated with antibiotics
b. nursing home patients transferred to the hospital
c. diabetics and HIV patients
d. patients having outpatient surgery
- CA-MRSA differs from HA-MRSA in all but which of the following:
a. mecA type
b. mechanism of resistance to methicillin
c. possession of toxins
d. PFGE type - A possible mechanism of resistance in VISA is
a. cell wall thickening by absorption of vancomycin
b. mutations in the chromosome coding for increased beta-lactamase
c. alteration of the PBP in the cell wall
d. increased export of vancomycin from the organism - The most important and practical process in controlling the spread of super
bugs is
a. rotating the use of antibiotics
b. wearing disposable gowns
c. universal gloving
d. hand hygiene - An organism with natural high resistance to antibiotics is
a. Escherichia coli
b. Staphylococcus aureus
c. Pseudomonas aeruginosa
d. Enterococcus faecalis - Increased colonization of the intestinal tract by VRE does not occur with
a. use of antibiotics directed against intestinal anaerobes
b. use of vancomycin as growth promoter in animals
c. intestinal non-absorption of vancomycin when high levels are administered
d. use of cephalosporins that inhibit growth of normal intestinal bacteria - The most reliable identification of MRSA infection requires
a. a presence of PBP2a and MICs between 2-8 µg/ml
b. molecular detection of the mecA gene
c. growth of Staphylococcus aureus on an oxacillin agar screen
d. a positive MRSA screen by latex agglutination - Laboratory identification of VRE includes
a. determining the presence of vanC gene
b. MHA with 6 µg/ml of oxacillin added as a screen
c. agar screen test followed by disk diffusion test
d. BHIA with 6 µg/ml of vancomycin added as a screen - Laboratory screening for VISA and VRSA
a. should be done on all MRSA isolates
b. is best performed by an automated susceptibility testing system
c. requires broth dilution by a reference laboratory
d. means determining the presence of the mecA and vanA genes - Epidemiologic methods found CA-MRSA potentially the cause of more severe
disease than HA-MRSA because
a. mecA Type IV has a greater effect than Type II
b. of the presence of more toxins and virulence factors
c. antibiotic patterns of sensitivity were different
d. cross-transmission is more likely in the community - Of the following, which is a likely cause of mistaken MRSA detection
a. use of automated systems and disk diffusion
b. specimen contamination in material cultured from a non-sterile site
c. use of PCR in-house assay
d. broth dilution by AB Biodisk's E test® - Protecting the community against the spread of super bugs involves all the
following except
a. confirming diagnosis with culture and reporting resistant strains to Public Health Department
b. adhering to universal precautions by health care providers
c. widespread use of prophylactic antibiotics
d. informing the community of methods to prevent spread in crowded conditions
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