Drug-Resistant Superbugs, Multi-drug Resistant Organisms: MRSA, VRE, Clostridium difficile, and CRE
Assume you perform microbiology for an institution submitting surveillance cultures for MRSA. Which isolate should receive further workup to rule out methicillin (oxacillin) resistance? Please select the single best answer On Baird Parker, a gray brownish colony with no clear zone. Gram-positive cocci in clusters, catalase positive.Black colonies on Chromagar. Catalase-positive, gram-positive cocci in clusters.Yellow colonies on mannitol salt agar; catalase-positive, coagulase-positive.Clear colonies on mannitol salt agar; catalase-positive, coagulase-negative.
On mannitol salt agar, S. aureus produces a yellow colony; catalase and coagulase reactions are positive. S. aureus on Baird Parker medium produces black colonies with a clear zone. There are different formulations of chromogenic agars for MRSA on the market, but the colors produced are described as either mauve or denim blue, depending on the product utilized.
When testing for C. difficile or its toxins, either a formed or liquid stool is an acceptable specimen. Select true or false TrueFalse
Only liquid stool samples should be processed. Due to the fact that the colonization rate is high, a positive result with a normal stool sample proves that the patient is colonized with C. difficile but not necessarily infected.
Which are true statements regarding HA-MRSA and CA-MRSA? Please select the single best answer Resistance for both strains is conferred by the mecA gene.HA strains tend to demonstrate resistance to more drug classes than CA strains.CA tends to be associated with the PVL gene and skin and soft tissue infections.All the above.
PBP2a, which has a reduced binding affinity for beta-lactams and remains active in cell wall synthesis even in the presence of beta-lactam antibiotics, is coded by the mecA gene. Both HA and CA strains of MRSA possess the mecA gene, although CA strains typically possess a smaller variant of that gene. CA strains may be susceptible to some antibiotics that HA strains are resistant to. CA strains are also associated with the PVL gene, which code for enzymes that produce tissue necrosis and leukocyte destruction.
Pseudomembranous colitis (PMC) is an inflammatory disease of the colon caused by toxins of which of these organisms? Please select the single best answer Staphylococcus aureusEnterococcus faeciumClostridium difficile
PMC is an inflammatory disease of the colon caused by toxins of C. difficile. C. difficile produces two potent toxins: Toxin A (TcdA), an enterotoxin and Toxin B (TcdB), a cytotoxin. It is the production of these toxins in the gastrointestinal tract that ultimately leads to disease. There is a relationship between toxin levels, the development of PMC, and the duration of diarrhea.
The increased resistance of MRSA strains to beta-lactam antibiotics is due to production of which of the following penicillin binding proteins (PBPs)? Please select the single best answer PBP 2PBP 2aPBP 3PBP 4
The beta-lactam resistance of MRSA is determined by the production of a novel penicillin-binding protein called PBP 2a (PBP 2'), that has a reduced binding affinity for beta-lactam antibiotics. This allows MRSA strains to continue cell wall synthesis due to the uninhibited activity of PBP2a even in the presence of otherwise inhibitory concentrations of beta-lactam antibiotics. The mecA gene encodes the production of PBP 2a. S. aureus intrinsically produces beta-lactamase enzymes that break down beta-lactam antibiotics; these are designated PBP 1 - 4.
Which one of these characteristics distinguishes vancomycin-resistant Enterococcus faecium and E. faecalis from other Enterococcus species? Please select the single best answer PYR positive reactionNon-motilityCatalase negativeGrowth on bile esculin agar
The characteristic that distinguishes vancomycin-resistant E. faecium and E. faecalis from other Enterococcus species is their lack of motility. Enterococci are all catalase-negative. Growth on bile esculin agar and in 6.5% salt broth are two characteristics that have commonly been used to identify Enterococcus to the genus level. A positive esculin in combination with a positive PYR reaction is another approach to presumptive identification.
New Delhi metallo-beta-lactamase (NDM) is the most common carbapenemase produced among CRE in the United States. Select true or false TrueFalse
The production of Klebsiella pneumoniae carbapenemase (KPC) is currently the most common carbapenemase among CRE in the United States. KPC is most commonly encountered on plasmids in K. pneumoniae isolates, but can also occur with K. oxytoca, Enterobacter species, E. coli, Citrobacter freundii, Salmonella species, Serratia species, and other gram-negative bacilli. NDM is the most common metallo beta-lactamase (MBL) worldwide; frequently encountered in India and Pakistan. Of the different types of beta-lactamases with carbapenemase activity, the MBLs are of the greatest concern globally. This is because MBLs were previously only found in Pseudomonas aeruginosa. Recently, reports of Klebsiella pneumoniae that produce MBLs now have scientists concerned with new transmissible carbapenem resistance mechanisms that are occurring in Enterobacteriaceae.
Moving forward, important strategies for dealing with MRSA strains will include which of the following? Please select the single best answer Antimicrobial stewardship to guide the use of both existing alternatives and newer drugs.Identification of MRSA strains in all settings (inpatient as well as outpatient).Possible development of vaccines.All the above.
Prompt identification of an MRSA strain, appropriate utilization of antimicrobial therapy - for both the treatment of identified infections, as well as reducing the induction of further resistance - and reducing the transmission of resistant strains, requires a proactive approach by laboratorians, infection control practitioners, physicians, and pharmacists. Vaccines may offer promise in the future, but will not replace our coordinated efforts.
The pathogenicity of S. aureus, as well as the frequency with which this organism produces infections, can be attributed to: That's partially correct. The correct answers are highlighted below Exfoliative toxin and enterotoxinsA porous cell wallNatural colonization/reservoir for infectionHyaluronidase
S. aureus colonizes approximately 25 - 30 % of the general population, providing significant reservoirs of organism for transmission. In addition, it produces a number of different enzymes and toxins, including (but not limited to) exfoliative toxin, enterotoxins, hyaluronidase and lipase, and beta lactamases. The cell wall of S. aureus is not porous. Structural components of its cell wall function as a protective barrier, aid in adherence to mucous membranes, and allow the organism to resist phagocytosis.
A laboratory performs MIC tests, in addition to Kirby Bauer, and a PBP 2a assay on blood culture isolates. Which of the following isolates should be reported as oxacillin-resistant? More than one answer is correct. Please select all correct answers Positive PBP 2a; cefoxitin zone = 17 mm; oxacillin MIC = 4 ug/ml.PBP 2a not performed; cefoxitin zone = 25 mm; oxacillin MIC = 0.5 ug/ml.Negative PBP 2a; cefoxitin zone = 22 mm; oxacillin MIC = 1 ug/ml.Negative PBP 2a; cefoxitin zone = 22 mm; oxacillin MIC = 4 ug/ml.
A positive PBP 2a assay, a cefoxitin zone size of < 21 mm, or an oxacillin MIC of > 4 ug/ml all confer the interpretation of oxacillin resistance (MRSA). If the PBP 2a assay is negative, the cefoxitin disc is susceptible, but the oxacillin MIC is equal to or greater than 4, the isolate should be reported as oxacillin resistant; resistance mechanisms other than mecA may be present.
A laboratory's primary susceptibility testing method is disk diffusion. The cefoxitin disc has a zone size of 19 mm and the vancomycin disc has a zone size of 7 mm. Which of the following are appropriate courses of action? More than one answer is correct. Please select all correct answers Report the isolate as oxacillin resistant and vancomycin susceptible.Report the isolate as oxacillin resistant and suppress the vancomycin result.Repeat the disc diffusion test; if results verify, perform or refer the isolate for vancomycin MIC testing.If in-house vancomycin MICs are greater than or equal to 4 µg/mL, refer isolate to a reference laboratory.
According to CLSI documents, disk diffusion adequately detects vancomycin resistance (van A). These isolates will have no zone of inhibition (zone = 6mm). Isolates producing a zone size > 7 mm should not be reported as susceptible without performing a vancomycin MIC; follow-up on these isolates is critical for both therapeutic and infection control considerations.
Which of these describes the mode of action of the beta-lactam class of antibiotics? You answered the question correctly. The correct answer is highlighted below Inhibits protein synthesisInhibits DNA synthesisInhibits cell wall synthesisInhibits RNA synthesis
Antibiotics inhibit bacterial growth by interfering with one or more cellular processes. The beta-lactam antibiotics act to inhibit the formation cell wall formation. Aminoglycosides inhibit protein synthesis (by binding to the bacterial ribosome); quinolones inhibit DNA synthesis, and Rifampin inhibits RNA synthesis.
Based on the Centers for Disease Control and Prevention's (CDC's) definition, which statement describes a carbapenemase-resistant Enterobacteriaceae (CRE)? Please select the single best answer Any Klebsiella pneumoniae isolate, regardless of antimicrobial susceptibility testing (AST) results, is considered CRE.Any Enterobacteriaceae isolates that are resistant to any carbapenem drug during AST are considered CRE.Any Proteus isolates are considered CRE due to intrinsic nonsusceptibility to imipenem (one of the carbapenem antimicrobials).
As of January 2015, carbapenem-resistant Enterobacteriaceae (CRE) are defined by the CDC ) to include Enterobacteriaceae isolates that are: Resistant to any carbapenem antimicrobial (imipenem*, meropenem, doripenem, or ertapenem) OR Documented to possess a carbapenemase *Note that in organisms that are intrinsically nonsusceptible to imipenem (eg, Proteus species), the organism must show resistance to a carbapenem other than imipenem.
Which of the following enzymes, produced by S. aureus, is responsible for preventing penicillin antibiotics from being effective against a Staph infection? Please select the single best answer Beta-lactamaseCoagulaseCatalaseHyaluronidase
Beta-lactamase is the enzyme, produced by S. aureus, that is responsible for preventing penicillin antibiotics from being effective against a Staph infection. Beta-lactamase breaks down the beta-lactam antibiotics (eg, penicillins, cephalosporins, carbapenems, monobactams), allowing S. aureus to be resistant to these antibiotics. Catalase distinguishes staphylococci from streptococci. The production of coagulase distinguishes S. aureus from other staphylococci. Hyaluronidase aids S. aureus in skin colonization/infection spread.
Which of the following statements concerning C. difficile is NOT true? You answered the question correctly. The correct answer is highlighted below It is the causative agent of an inflammatory condition of the large intestine.It is an aerobic organism.It produces potent toxins.It produces spores.
C. difficile is an anaerobic organism found in the large intestine of approximately 3% of the population. It is the causative agent of an inflammatory condition of the large intestine. C. difficile produces two potent toxins: Toxin A (TcdA), an enterotoxin and Toxin B (TcdB), a cytotoxin. It is the production of these toxins in the gastrointestinal tract that ultimately leads to disease. Large gram-positive bacilli with spores will be observed on a Gram stain of a typical C. difficile colony.
C. difficile disease is more likely to occur when: More than one answer is correct. Please select all correct answers The balance of the gastrointestinal flora is altered by previous antibiotic therapy.The patient has previously been hospitalized.The patient has been previously treated at an orthopedic sports clinic.The patient has a chronic health condition.
C. difficile is frequently present in the environment (including those of hospital wards.) If spores or organisms are ingested, they may be able to survive the acidity of the stomach. The likelihood of colonization and/or infection is increased by factors that alter the normal gastrointestinal flora, and allow the organism to proliferate. Underlying disease along with a weakened immune system increase the likelihood of these scenarios.
___________ is predominantly associated with skin and soft tissue infections (SSTIs), such as abscesses, cellulitis, folliculitis, and impetigo. Please select the single best answer HA-MRSACA-MRSA
CA-MRSA infections are predominantly skin and soft tissue infections (SSTIs), such as abscesses, cellulitis, folliculitis, and impetigo.
Which of the following is a selective media recommended for the isolation of C. difficile? Please select the single best answer Cefoxitin-cycloserine-fructose agar (CCFA)Buffered-charcoal yeast extract(BCYE) agarKanamycin Vancomycin laked blood (LKV) agarThiosulphate citrate bile salts sucrose (TCBS) agar
CCFA is a differential/selective agar recommended for the isolation of C. difficile from stool samples. There is however, no distinction between pathogenic and commensal strains, which all produce yellow colonies with a characteristic "ground glass" appearance.
With regards to identifying resistance in enterococci, which general statements are true? That's partially correct. The correct answers are highlighted below Both disk diffusion and broth microdilution tests should be incubated a full 24 hours to detect vancomycin resistance.BHI agar with 6 µg/mL vancomycin can be employed as a screening methodology for vancomycin resistance.All antibiotics on a gram-positive panel should be reported.Methodologies employed should also address the detection of high level resistance to gentamicin and streptomycin.
CLSI provides the definitive guidelines for detection of resistance in enterococci. BHI with 6 µg/mL vancomycin can be employed as a screening methodology for vancomycin resistance; the presence of >1 colony indicates the need for further testing to confirm potential resistance. All screening and susceptibility tests require a full 24 hours incubation. Since the standard approach for treating systemic infections with enterococci is a combination of a cell wall drug with an aminoglycoside, testing protocols should also address the detection of high level resistance to gentamicin and streptomycin. CLSI criteria for reporting antibiotics should be strictly adhered to. Since the enterococci possess many intrinsic resistance factors, there are many antibiotics that should not be included in the final report.
Detection of the mecA gene in a clinical isolate of S. aureus is an indication of resistance to which of these antibiotics?
Detection of mecA in a clinical isolate of S. aureus is an indication of resistance to oxacillin.
Enterococci can possess both intrinsic and acquired resistance. Which of the following represents the intrinsic resistance of a typical enterococcal strain? More than one answer is correct. Please select all correct answers High level resistance to glycopeptidesAminoglycoside resistanceResistance to clindamycin and trimethoprim-sulfamethoxazoleResistance to cephalosporins
Enterococci are intrinsically resistant to many cephalosporins, clindamycin, trimethoprim-sulfamethoxazole, and aminoglycosides. CLSI contraindicates reporting any of these drugs as susceptible because these interpretations will not predict in vivo response. Glycopeptide resistance, as well as high level aminoglycoside resistance, are acquired mechanisms that create diagnostic, infection control, and therapeutic concerns. Enterococci are intrinsically resistant to many antibiotics. Intrinsic resistance affects not only beta lactams (including a broad range of cepahlosporins) and aminoglycosides, but also clindamycin and trimethoprim/sulfamethoxazole. The standard recommended therapy for systemic infections is a combination of either penicillin or vancomycin and an aminoglycoside (gentamicin or streptomycin). The goal of combination therapy is to achieve a synergistic bactericidal effect between the cell wall agent and the aminoglycoside.In recent decades, increasing resistance to other antibiotics through acquired resistance mechanisms has become a growing therapeutic and infection control problem. Of key concern are high level resistance (HLR) to aminoglycosides and increasing resistance to glycopeptides such as vancomycin.
Which of the following statements reflect accurate identifications of Enterococcus species? More than one answer is correct. Please select all correct answers Gram-positive cocci in chains, catalase negative, esculin positive, PYR negative: Enterococcus species.Gram-positive cocci in pairs, catalase negative, esculin positive, PYR positive, vancomycin intermediate, nonmotile, nonpigmented: E. gallinarum.Gram-positive cocci in pairs or chains, catalase negative, black colonies on bile esculin agar, growth in 6.5% salt broth: Enterococcus species.Gram-positive cocci in pairs or chains, catalase negative, esculin positive, PYR positive, vancomycin intermediate, motile, yellow pigment: E. casseliflavus.
Enterococci can be identified to genus level by several methods; two examples include growth on bile esculin agar coupled with growth in 6.5% salt broth, and the combination of a positive esculin and positive PYR reaction. When vancomycin intermediate or resistant strains are encountered, motility and the presence of pigment can help rule out species where intrinsic, rather than acquired, resistance is present. Both E. gallinarum and E. casseliflavus are motile. In addition, E. casseliflavus possesses a yellow pigment.
When using current antimicrobial susceptibility testing (AST) breakpoints, it is recommended by CLSI that laboratories should also routinely implement testing, such as the modified Hodge test (MHT) or Carb NP test (CNPt), to detect the presence or absence of carbapenemase. Select true or false TrueFalse
If the most current AST breakpoints are in use, testing to detect the presence or absence of carbapenemase is only recommended for epidemiological (eg, in an effort to gain a better understanding of emerging resistance patterns) or infection control purposes (eg, when a CRE outbreak is suspected), not for routine patient isolate testing.
What carbapenemase is produced most commonly by CRE encountered in the United States? Please select the single best answer The production of AmpC beta-lactamaseThe production of Klebsiella pneumoniae carbapenemase (KPC)The production of oxacillin (OXA) carbapenemaseThe production of metallo-beta lactamase (MBL)
In the United States, the production of KPC enzymes are the most commonly encountered carbapenemase. This mechanism of resistance among CRE is found mostly in Klebsiella pneumoniae isolates, but is also found in K. oxytoca, Enterobacter species, E. coli, Citrobacter freundii, Salmonella species, Serratia species, and other gram-negative bacilli (eg, Pseudomonas aeruginosa). the emergence of carbapenemase-producing strains. Carbapenem resistance among Enterobacteriaceae can be due to several different mechanisms, including the production of beta-lactamase (eg, AmpC, ESBLs, or MBLs) which, when combined with porin loss, limits entry of the carbapenem into the cell and can render an organism nonsusceptible. The AmpC beta-lactamases (a cephalosporinase) and the ESBLs are non-carbapenemases. OXA is a carbapenemase that is relatively rare in the US, but commonly encountered in Africa and Europe. MBL is a carbapenemases, but is uncommon in the US. Of the MBLs, New Deli MBL (NDM) is the most common MBL worldwide, frequently encountered in India and Pakistan. The MBL carbapenemases are of the greatest concern, because they were previously only found in Pseudomonas aeruginosa. Recently, reports of Klebsiella pneumoniae that produce MBLs now have scientists concerned with new transmissible carbapenem resistance mechanisms that are occurring in Enterobacteriaceae.
Which statement regarding carapenemase-resistant Enterobacteriaceae (CRE) is true? Please select the single best answer The use of current breakpoints in antimicrobial susceptibility testing (AST) is the best detection method for CREs.The modified Hodge test (MHT) should be performed routinely on all Enterobacteriaceae recovered from clinical isolates to detect the presence of carbapenemase.When performing antimicrobial susceptibility testing (AST) on possible CRE isolates, it can be assumed that current AST breakpoints are in place when using a commercially-available automated AST system.Patients with CRE can be treated with a vast number of antimicrobial agents.
It is true that the best way to detect CRE is to ensure the use of current AST breakpoints. Detecting the presence of carbapenemase in CRE isolates is not routinely recommended for patient care. However, there may be facility infection control procedures or epidemiological reasons that may warrant detecting the presence of carbapenemase, including when a CRE outbreak is suspected or in an effort to gain a better understanding of emerging resistance patterns. The routine use of tests used to detect the presence of carbapenemase, such as the MHT, would certainly not be performed on all Enterobacteriaceae recovered from clinical isolates. Regarding the use of commercially available AST systems, it is best to contact the manufacturer to verify the breakpoint status used. Given the critical impact of CRE on public health, assumptions must not be made. Patients with CRE have very limited antimicrobial treatment options, including polymyxins, tigecycline, minocycline, aminoglycosides (except tobramycin), fosfomycin, and ceftazidime/avibactam (only for class A producers). Pan-resistant strains have been reported that have developed resistance to all currently available antibiotics.
MRSA is only a problem for patients who are hospitalized. Select true or false TrueFalse
MRSA has been present in hospital settings (HA-MRSA) for several decades. However, MRSA strains have emerged outside the hospital in community settings among otherwise healthy individuals. These strains are referred to as community-associated MRSA (CA-MRSA), and they now account for the majority of staphylococcal infections seen in the hospital emergency department or in clinics.
Which of these gene phenotypes is found most often in vancomycin-resistant strains of Enterococcus faecium? Please select the single best answer VanAVanBVanC
Most vancomycin resistant E. faecium strains possess the VanA gene. The VanA phenotype has an inducible high level resistance to vancomycin as well as teicoplanin (encoded by the VanA gene). The VanB phenotype (encoded by two vanB genes) has moderate to high resistance to vancomycin only. The VanC phenotype (encoded by two vanC genes) demonstrates a non-inducible low level resistance to vancomycin.
Which of the following scenarios represents appropriate detection of MRSA by the Kirby Bauer method? Please select the single best answer Mueller-Hinton agar (MHA); direct colony suspension; 37°C; cefoxitin disk; 24 hour incubationMHA; direct colony suspension; 35°C; oxacillin disk; 24 hour incubationMHA; direct colony suspension; 35°C; cefoxitin disk; 18 hour incubationMHA; direct colony suspension; 35°C; cefoxitin disk; 24 hour incubation
Mueller-Hinton agar is the standard medium for Kirby Bauer testing on Staphylococcus isolates. The direct colony suspension method, utilizing a 0.5 McFarland standard, should be used to prepare the inoculum. A full 24-hour incubation is required. A 30 µg cefoxitin disk is recommended to detect mecA mediated resistance. Incubation above 35°C may not allow for the detection of resistance.
Which of these organisms is associated with the condition known as toxic shock syndrome? Please select the single best answer Clostridium difficileStaphylococcus aureusEnterococcus faecalis
S. aureus infections range from superficial, localized skin infections, such as folliculitis, to deeper, more serious skin lesions and the more serious toxin mediated conditions - scalded skin syndrome and toxic shock syndrome.
Various methods have been employed for detection of C. difficile disease: cultivation of the organism, cell cytotoxin neutralization assays, and enzyme immunoassays have all been among the staples of diagnostic approaches. Which statements are accurate characterizations of these assays? More than one answer is correct. Please select all correct answers Cultivation on CCFA agar is relatively easy to perform and is uniformly diagnostic.Cell culture based cytotoxin neutralization assays provide definitive detection of toxin-producing C. difficile strains.Enzyme immunoassays detecting Toxin A provide adequate detection and more efficient methodologies compared to culture or cell culture based assays.Enzyme immunoassays detecting both Toxin A and Toxin B allow the detection of more strains of C. difficile and are therefore preferred over assays that detect only Toxin A.
Stool culture is very effective in detecting C. difficile, although it requires up to four days to isolate the organism. Isolates must also be subsequently tested for toxin production to prove their causal relationship to disease. Enzyme immunoassays provide a more efficient and rapid means of diagnostic testing. Sensitivity of detection is enhanced by choosing a method that allows for detection of both toxins A and B. Although cell culture based cytotoxicity neutralization assays have been considered the gold standard, they are labor intensive and require at least 48 hours incubation.
Which of the following approaches for diagnostic testing have been indicated by recent literature? More than one answer is correct. Please select all correct answers Molecular methods for the detection of the tcd geneGlutamate dehydrogenase (GDH) detection as a stand-alone methodologyGDH assays, followed up by a second assay for toxin production
Studies have shown that assays for GDH production provide a sensitive screening method for the detection of C. difficile. A second assay for detection of toxin is required in GDH algorithms. Increasing focus is being placed on molecular methods as a possible alternative for a both highly sensitive, specific, and rapid method. A negative GDH result has a high negative predictive value; but a positive result is not always associated with a toxin producing strain.
PBP2a is the altered penicillin-binding protein responsible for resistance of MRSA strains to the beta-lactam class of antibiotics. Select true or false TrueFalse
This statement is true. PBP2a encoded by the gene mecA is an altered penicillin-binding protein with low affinity for the beta-lactams so that cell wall synthesis is unaffected by the presence of the drug.
Beta-lactam antibiotics interfere with cell wall synthesis by: Please select the single best answer Binding with a transpeptidasePreventing the final stage of peptidoglycan synthesisInterfering with PBPsAll of the above
Transpeptidase enzymes catalyze the final stage of peptidoglycan synthesis during cell wall formation. Beta-lactam antibiotics bind with these enzymes, interfering with their function. The transpeptidase enzymes are also referred to as PBP's, or penicillin-binding proteins.
Which statements concerning vancomycin resistance in Enterococci are true? More than one answer is correct. Please select all correct answers Van A and Van C are the most clinically significant phenotypes.Van B confers intrinsic low level resistance to vancomycin only.Low level vancomycin resistance is characteristic of E. gallinarum and E. casseliflavus.Both ampicillin and vancomycin resistance are found more frequently in E. faecium than in E. faecalis.
Van C confers low level intrinsic resistance to vancomycin and are characteristic in E. gallinarum and E. caseliflavus. Both ampicillin and vancomycin resistance are more frequently encountered in E. faecium than in E. faecalis. Of the six described phenotypes of glycopeptide resistance in enterococci, Van A and Van B are the most clinically significant. Van A confers high level resistance to both vancomycin and teicoplanin; Van B confers moderate to high resistance to vancomycin only.