Vancomycin-resistant Entercocci – Essay Example
Vancomycin-resistant Entercocci – Essay Example
The infection usually occurs after an introduction of the bacteria into a preciously sterile environment. A procedure such as in-dwelling catheters, cardiothoracic surgery, transplants and extended stays in ICU wards increases the risk of acquiring VRE. One method of transfer was discovered in the use of a suction device that removes oral and nasal secretions common in the ICU and Yankauer Catheters. (Kayyali 2006 para 1)
VRE also spreads easily by computer keyboards with or without covers. Since most health care documentation is done electronically, this is a serious concern in all areas of the hospital, but in particular, critical care units. Long Term Care facility (LTC) patients are also at risk. VRE and Methacillin Resistant Staphyloccos Aureus (MRSA) have been shown to survive on keyboards for an hour and on covers for five minutes. Bare hands transferred the bacteria at a considerably higher percentage than gloved hands. (Computer Bugs)
As a bio-terrorist weapon VRE is attractive due to easy access and the ease of transmission, especially in hospital settings and LTC facilities where patients come into contact with outsider visitors. Vancomycin-resistant Entercocci – Essay Example.Hospital and LTC facility patients carry a higher risk of contracting VRE infections due to conditions that inhibit their immune systems.
The disturbing fact that VRE has been shown in one laboratory case to spread genetic mutation to MRSA, makes VRE an excellent weapon choice for bio-terrorists. If MRSA were to become resistant to Vancomycin….
Long Term Care facility (LTC) patients are also at risk. VRE and Methacillin Resistant Staphyloccos Aureus (MRSA) have been shown to survive on keyboards for an hour and on covers for five minutes. Bare hands transferred the bacteria at a considerably higher percentage than gloved hands. (Computer Bugs, 2005 pg 1)
As a bio-terrorist weapon VRE is attractive due to easy access and the ease of transmission, especially in hospital settings and LTC facilities where patients come into contact with outsider visitors. Hospital and LTC facility patients carry a higher risk of contracting VRE infections due to conditions that inhibit their immune systems.
The disturbing fact that VRE has been shown in one laboratory case to spread genetic mutation to MRSA, makes VRE an excellent weapon choice for bio-terrorists. If MRSA were to become resistant to Vancomycin it would be untreatable. (CHA 1996 pg 2)
In the United States acquisition and transference of VRE outside hospital settings is not supported by data. Colonization nearly always precedes the majority of infections in European studies, which indicates that colonization occurs in the community. European reports also show that,”VRE exists in animal feces and in human foods originating in animals.” (McDonald, 1997 para 3). This implies a relationship between the community and nosocomical infections.
The most common form of Entercocci is E. faecalis, responsible for 80% of colonizational human infections. As a possible weapon Entercocci are ideal in that they are an extremely resilient bacteria able to withstand wide temperature ranges, hypertonic, hypotonic, acidic and alkaline environment.Vancomycin-resistant Entercocci – Essay Example. Entercocci grow under reduced or oxygenated conditions and can tolerate solutions of bile salts that kill
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Vancomycin-Resistant Enterococci (VRE) are on the rise worldwide. Here, we report the first prevalence of VRE in Nigeria using systematic review and meta-analysis. International databases MedLib, PubMed, International Scientific Indexing (ISI), Web of Science, Scopus, Google Scholar, and African journals online (AJOL) were searched. Information was extracted by two independent reviewers, and results were reviewed by the third. Two reviewers independently assessed the study quality using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. OpenMeta analyst was used. The random effect was used, and publication bias was assessed using a funnel plot. Between-study heterogeneity was assessed, and the sources were analysed using the leave-one-out meta-analysis, subgroup analysis, and meta-regression. Nineteen studies met the eligibility criteria and were added to the final meta-analysis, and the study period was from 2009–2018. Of the 2552 isolates tested, 349 were VRE, and E. faecalis was reported the most. The pooled prevalence of VRE in Nigeria was estimated at 25.3% (95% CI; 19.8–30.8%; I2 = 96.26%; p < 0.001). Between-study variability was high (t2 = 0.011; heterogeneity I2 = 96.26% with heterogeneity chi-square (Q) = 480.667, degrees of freedom (df) = 18, and p = 0.001). The funnel plot showed no publication bias, and the leave-one-out forest plot did not affect the pooled prevalence. The South-East region had a moderate heterogeneity though not significant (I2 = 51.15%, p = 0.129). Meta-regression showed that all the variables listed contributed to the heterogeneity except for the animal isolate source (p = 0.188) and studies that were done in 2013 (p = 0.219). Adherence to proper and accurate antimicrobial usage, comprehensive testing, and continuous surveillance of VRE are required.
After they were first identified in the mid-1980s, vancomycin-resistant enterococci (VRE) spread rapidly and became a major problem in many institutions both in Europe and the United States. Since VRE have intrinsic resistance to most of the commonly used antibiotics and the ability to acquire resistance to most of the current available antibiotics, either by mutation or by receipt of foreign genetic material, they have a selective advantage over other microorganisms in the intestinal flora and pose a major therapeutic challenge. The possibility of transfer of vancomycin resistance genes to other gram-positive organisms raises significant concerns about the emergence of vancomycin-resistant Staphylococcus aureus. We review VRE, including their history, mechanisms of resistance, epidemiology, control measures, and treatment. Vancomycin-resistant Entercocci – Essay Example.
Enterococci were originally classified as enteric gram-positive cocci and later included in the genus Streptococcus (185). In the 1930s, with the establishment of the Lancefield serological typing system, enterococci were classified as group D streptococci and were differentiated from the nonenterococcal group D streptococci such as Streptococcus bovis by distinctive biochemical characteristics (149). Sherman further recommended that the term “enterococcus” should be used specifically for streptococci that grow at both 10 and 45°C, at pH 9.6, and in 6.5% NaCl and survive at 60°C for 30 min (232). These organisms were also noted to hydrolyze esculin in the presence of bile. In the 1980s, based on genetic differences, enterococci were removed from the genus Streptococcus and placed in their own genus, Enterococcus (228). The previously used species designations such as faecalis, faecium, durans, and so forth were retained but were preceded by the genus name Enterococcus in place of Streptococcus. Although a dozen Enterococcus species have been identified, only two are responsible for the majority of human infections. Until recently, E. faecalis had been the predominant enterococcal species, accounting for 80 to 90% of all clinical isolates, and E. faecium had accounted for 5 to 15% (110, 158, 173, 204, 219). Other Enterococcus species (E. gallinarum, E. casseliflavus, E. durans, E. avium, and E. raffinosis) are isolated much less frequently and account for less than 5% of clinical isolates (110, 158, 173, 204, 219).
Enterococci have been recognized as an important cause of endocarditis for almost a century. In addition to this long-established role, enterococci began to be recognized as common causes of hospital-acquired infections in the middle to late 1970s. This was coincident with and probably related to the increasing use of third-generation cephalosporins to which enterococci are naturally resistant (185). Enterococci are currently ascendant nosocomial pathogens, having become the second most common organisms recovered from nosocomial urinary tract and wound infections and the third most common cause of nosocomial bacteremia in the United States (227). One of the major reasons why these organisms have survived in the hospital environment is their intrinsic resistance to several commonly used antibiotics and, perhaps more important, their ability to acquire resistance to all currently available antibiotics, either by mutation or by receipt of foreign genetic material through the transfer of plasmids and transposons (Table (Table1)1) (53). Vancomycin-resistant Entercocci – Essay Example. Therapeutic difficulties presented by enterococci were well recognized as early as the 1950s, when response rates of enterococcal endocarditis to penicillin used alone were found to be markedly lower than those of streptococcal endocarditis (73, 77). Because most enterococci are tolerant to the bactericidal activity of β-lactam and glycopeptide antibiotics, bactericidal synergy between one of these antibiotics and an aminoglycoside is needed to treat most serious enterococcal infections such as endocarditis and meningitis (144, 175). Since the duration of therapy is longer and the toxicity of the combination regimens is increased compared to those used for streptococcal endocarditis, enterococci are considered problem organisms with respect to antimicrobial therapy (186). The synergistic bactericidal effect between aminoglycosides and β-lactam or glycopeptide antibiotics is lost if there is high-level resistance to either class of drug. Resistance to high concentrations of aminoglycoside antibiotics is usually mediated by aminoglycoside-modifying enzymes, and it is widespread among enterococci (more than 50% of isolates in some centers show this resistance) (267). Also, many isolates of E. faecium are highly resistant to penicillins, because their penicillin binding proteins (PBP) have low affinity for penicillins (113). Until recently, vancomycin was virtually the only drug that could be consistently relied on for the treatment of infections caused by multidrug-resistant enterococci.
TABLE 1
Intrinsic and acquired antimicrobial drug resistance in enterococcia
| Intrinsic resistance |
| β-Lactams (particularly cephalosporins and penicillinase-resistant penicillins) |
| Low concentrations of aminoglycosides |
| Clindamycin |
| Fluoroquinolones |
| Trimethoprim-sulfamethoxazole |
| Acquired resistance |
| High concentrations of β-lactams, through alteration of PBPs or production of β-lactamase |
| High concentrations of aminoglycosides |
| Glycopeptides (vancomycin, teicoplanin) |
| Tetracycline |
| Erythromycin |
| Fluoroquinolones |
| Rifampin |
| Chloramphenicol |
| Fusidic acid |
| Nitrofurantoin |
Vancomycin had been in clinical use for more than 30 years without the emergence of marked resistance (129). Teicoplanin is another glycopeptide antibiotic; it is not available in the United States but has been used in Europe. Because of their activity against methicillin-resistant staphylococci and other gram-positive bacteria, these drugs have been widely used for therapy and prophylaxis against infections due to these organisms (109). Oral vancomycin, which is poorly absorbed, has been used extensively for the treatment of Clostridium difficile enterocolitis.
In 1988, Uttley et al. were the first to report the isolation of vancomycin-resistant E. faecalis and E. faecium in England (248). Shortly after the first isolates of vancomycin-resistant enterococci (VRE) were reported by investigators in the United Kingdom and France (155, 248), similar strains were detected in hospitals located in the eastern half of the United States (104). Subsequently, VRE have spread with unanticipated rapidity and are now encountered by hospitals in most states (31, 43, 134). Vancomycin-resistant Entercocci – Essay Example.
MECHANISMS OF RESISTANCE
β-Lactam Resistance
Complete or relative resistance to β-lactams is a characteristic feature of the genus Enterococcus. E. faecalis is typically 10 to 100 times less susceptible to penicillin than are most streptococci, while E. faecium is at least 4 to 16 times less susceptible than E. faecalis (185). While most isolates of E. faecalis are inhibited by concentrations of penicillin or ampicillin (1 to 8 μg/ml) easily achievable in humans, isolates of E. faecium usually require an average of 16 to 64 μg/ml to inhibit growth, although some isolates are even more resistant (186). An additional problem with enterococci is that they are typically tolerant to β-lactams (i.e., MBC/MIC of >32). The major mechanism underlying this resistance has been the production of low-affinity PBP (95). Penicillin resistance is directly proportional to the amount of PBP5 (a specific PBP) produced (259). Fontana et al. showed that loss of the ability of a strain of E. faecium to produce PBP5 caused this highly penicillin-resistant strain to become hypersusceptible to penicillin (97). β-Lactamase-producing enterococci are infrequently isolated (182). Unlike most staphylococci, where β-lactamase production is inducible, β-lactamase production in enterococci is constitutive, low level, and inoculum dependent (127, 182).
Aminoglycoside Resistance
Early studies demonstrated that two types of streptomycin resistance occur in enterococci: (i) moderate-level resistance (MIC, 62 to 500 μg/ml), because of low permeability, which can be overcome with a penicillin (which increases the cellular uptake of the aminoglycoside); and (ii) high-level resistance (MIC, ≥2,000 μg/ml), which is either ribosomally mediated or due to the production of aminoglycoside-inactivating enzymes (171). Since enterococcal resistance to gentamicin and streptomycin occur by different mechanisms, it is important to test susceptibilities to both agents. Gentamicin resistance is predominantly the result of the presence of the inactivating enzyme 2″-phosphotransferase-6′-acetyltransferase conferring resistance to gentamicin, tobramycin, netilmicin, amikacin, and kanamycin. Hence, gentamicin resistance is a good predictor of resistance to other aminoglycosides except streptomycin. Streptomycin resistance is encountered mainly in enterococcal strains that produce streptomycin adenyltransferase; these strains remain susceptible to gentamicin (127). Penicillin-aminoglycoside synergy does not occur in high-level aminoglycoside-resistant enterococci (streptomycin MIC, ≥2,000 μg/ml: gentamicin MIC, ≥500 μg/ml).
Vancomycin Resistance
Phenotypic description.
There are five recognized phenotypes of vancomycin resistance, VanA, VanB, VanC, VanD, and VanE (7, 94, 206). Two of these (VanA and VanB) are mediated by newly acquired gene clusters not previously found in enterococci. VanA and VanB resistance phenotypes were described primarily in E. faecalis and E. faecium. VanA-resistant strains possess inducible, high-level resistance to vancomycin (MICs, ≥64 μg/ml) and teicoplanin (MICs, ≥16 μg/ml) (Table (Table2)2) (7).Vancomycin-resistant Entercocci – Essay Example. Resistance can be induced by glycopeptides (vancomycin, teicoplanin, avoparcin, and ristocetin) and by nonglycopeptide agents such as bacitracin, polymyxin B, and robenidine, a drug used to treat coccidial infections in poultry (146). The details of vancomycin resistance have been best documented with the vanA gene cluster found on the transposon, or “jumping” genetic element, Tn1546 (7, 11). VanB isolates were initially believed to be inducibly resistant to more modest levels of vancomycin (MICs, 32 to 64 μg/ml) but are susceptible to teicoplanin. It is now known that levels of vancomycin resistance among VanB isolates may range from 4 to ≥1,000 μg/ml whereas susceptibility to teicoplanin is retained. VanB resistance determinants also reside on large mobile elements that can be transferred from one strain of enterococcus to another (212, 213). The VanC resistance phenotype was described in E. casseliflavus and E. gallinarum, which demonstrate intrinsic, low-level resistance to vancomycin (MICs, 4 to 32 μg/ml) and are susceptible to teicoplanin.
TABLE 2
Characteristics of phenotypes of glycopeptide-resistant enterococcia
| Characteristic | Phenotype
|
||||
|---|---|---|---|---|---|
| VanA | VanB | VanC | VanD | VanE | |
| Vancomycin MIC (μg/ml) | 64–>1,000 | 4–1,024 | 2–32 | 128 | 16 |
| Teicoplanin MIC (μg/ml) | 16–512 | ≤0.5 | ≤0.5 | 4 | 0.5 |
| Most frequent enterococcal species | E. faecium, E. faecalis | E. faecium, E. faecalis | E. gallinarum, E. casseliflavus, E. flavescens | E. faecium | E. faecalis |
| Genetic determinant | Acquired | Acquired | Intrinsic | Acquired | Acquired |
| Transferable | Yes | Yes | No | No | No |
Certain limitations of this classification method have become evident over time. For example, the genetic determinants of the VanA phenotype have now appeared in E. gallinarum and other enterococcal species (68). In a strain of E. avium, the VanA resistance determinants conferred a typical level of resistance to teicoplanin but low-level resistance to vancomycin (MIC, 16 μg/ml) (218). Additionally, mutants derived from VanB strains may exhibit resistance to teicoplanin and thus be phenotypically indistinguishable from VanA strains (126). Nevertheless, this phenotypic classification scheme is still useful, because it usually corresponds well to the genotypic classification and utilizes information that can be derived simply and inexpensively in a laboratory (80).
Genotypic classification and resistance mechanisms.
(i) Action of vancomycin on peptidoglycan synthesis.
Under normal conditions of peptidoglycan synthesis in enterococci, two molecules of d-alanine are joined by a ligase enzyme to form d-Ala–d-Ala, which is then added to UDP-N-acetylmuramyl-tripeptide to form the UDP-N-acetylmuramyl-pentapeptide. The UDP-N-acetylmuramyl-pentapeptide, when incorporated into the nascent peptidoglycan (transglycosylation), permits the formation of cross-bridges (transpeptidation) and contributes to the strength of the peptidoglycan layer (80). Vancomycin binds with high affinity to the d-Ala–d-Ala termini of the pentapeptide precursor units, blocking their addition to the growing peptidoglycan chain and preventing subsequent cross-linking (262, 265).Vancomycin-resistant Entercocci – Essay Example.
(ii) VanA glycopeptide resistance.
The vanA gene and other genes involved in the regulation and expression of vancomycin resistance (vanR, vanS, vanH, vanX, and vanZ) are located on a 10,581-bp transposon (Tn1546) of E. faecium, which often resides on a plasmid (11). Expression of these genes results in the synthesis of abnormal peptidoglycan precursors terminating in d-Ala–d-lactate instead of d-Ala–d-Ala. Vancomycin binds to d-Ala–d-Lac with markedly lower affinity than it does to the normal dipeptide product (37). The core protein functions favoring synthesis of pentadepsipeptide terminating in d-Ala–d-Lac are as follows. (i) VanA protein is a ligase of altered substrate specificity which produces d-Ala–d-Lac in preference to d-Ala–d-Ala (36). (ii) VanH protein is a d-hydroxy acid dehydrogenase which creates a pool of d-lactate for use in the above reaction (12). (iii) VanX protein is a d,d-dipeptidase lacking activity against d-Ala–d-Lac. This enzyme reduces pools of d-Ala–d-Ala produced by the native enterococcal ligase, thereby minimizing the competing synthesis of normal pentapeptide (215, 262).
VanA alone cannot confer resistance to vancomycin, probably because d-hydroxy acids such as d-Lac are neither natural products present in the environment of enterococci nor normally produced by enterococci (154). Thus, to synthesize d-lactate, enterococci must acquire the gene(s) within the vanA operon required to produce the substrate for VanA. VanH is responsible for the synthesis of d-lactate.
VanR and VanS proteins constitute a two-component regulatory system that regulates the transcription of the vanHAX gene cluster (8). VanS apparently functions as a sensor to detect the presence of vancomycin (7, 11) or, more likely, some early effect of vancomycin on cell wall synthesis (117). VanS then signals VanR, the response regulator, which results in activation, or turning on, of the synthesis of some other proteins (VanH, VanA, and VanX) involved in resistance. In VanA phenotype strains, either vancomycin or teicoplanin can induce the transcription, but the precise signals are still unknown (15). vanY and vanZ may contribute to but are not essential for resistance. VanY protein is a d,d-carboxypeptidase that cleaves the d-Ala terminal peptide from any normal peptide that may have been made, contributing modestly to resistance levels (53). VanZ modestly increases the MICs of teicoplanin but not of vancomycin, through mechanisms that have not yet been elucidated. It is not essential to the expression of the VanA phenotype.
Mapping of the vanA gene cluster from several U.S. isolates revealed some heterogeneity in organization (122, 123). Tn1546 existed intact in some strains but had insertion-like sequences between vanS and vanH in others. These vancomycin resistance gene clusters may be incorporated into even larger mobile elements containing additional insertion-like elements (122, 123).
Cross-linking of the precursors to the growing peptidoglycan is processed in bacteria by the PBPs, with PBP5 being used in enterococci (96). The replacement of d-Ala by d-Lac does not impair cross-linking of the modified precursors to the growing peptidoglycan chain. However, PBPs other than PBP5, which are so far not known to play a role in cell wall synthesis, are probably required for processing of the altered precursors (6). These high-molecular-weight PBPs display a higher affinity for β-lactams. Since VanA resistance is inducible, a shift in the PBPs occurs only in the presence of vancomycin and results in β-lactam hypersusceptibility. This effect explains the synergy displayed by the combination of the two classes of drugs against vancomycin-resistant strains.
(iii) VanB glycopeptide resistance.
VanB glycopeptide resistance in enterococci is mediated by an abnormal ligase (VanB) that is structurally related to VanA ligase (76% amino acid identity). VanB protein also favors the production of the pentadepsipeptide terminating in d-Ala–d-Lac (87). Genes analogous to their class A resistance counterparts are designated vanHB, vanXB, vanYB, vanRB, and vanSB (15). Levels of d,d-dipeptidase activity (VanXB) correlate with levels of vancomycin resistance (10). There is a high degree of sequence identity (approximately 70%) between VanHAX and VanHBBXB but considerably less homology (25 to 35% sequence homology) between the RS and Y proteins of VanA and VanB VRE (10, 86). There is no gene counterpart of vanZ in these organisms. vanYB is not found in all strains, and its position in the gene clusters differs from that of vanY in Tn1546 (9, 86). Recent reports have shown DNA sequence heterogeneity, suggesting three subtypes of the vanB ligase gene: vanB-1, vanB-2, and vanB-3 (60, 203, 208). The regulatory system in class B strains appears insensitive to induction by teicoplanin (10, 53). Teicoplanin induces the synthesis of VanA-related proteins but does not induce the production of VanB-related proteins. On the other hand, vancomycin induces the synthesis of the resistance proteins of both systems, and in fact, if a teicoplanin-susceptible enterococcus with the vanB gene cluster is preexposed to vancomycin, the strain then tests teicoplanin resistant as well. In addition, teicoplanin-resistant mutants can be derived from teicoplanin-susceptible, vanB-containing enterococci when these organisms are plated onto teicoplanin-containing agar. Such mutants can also arise in vivo during therapy (186). Possible mechanisms for teicoplanin resistance of these mutants include the loss of their requirement for an inducer (that is, if they constitutively produce high levels of the vancomycin resistance proteins) and the ability of teicoplanin to act as an inducer.Vancomycin-resistant Entercocci – Essay Example.
Another difference between VanA- and VanB-type resistance is that VanA is more widely distributed. It is by far the predominant type of resistance reported in Europe. While VanB strains are fairly common in the United States, with some hospitals reporting VanB exclusively, VanA still predominates (51). The vanA ligase gene, has also been found in a wider range of enterococcal species as well as in Corynebacterium spp., Arcanobacterium haemolyticum, and Lactococcus spp., while vanB has been found primarily in E. faecium and E. faecalis. The difference in the dissemination of these resistance traits may be related to the observation that the vanA gene cluster is often located on a transposon similar to Tn1546, which, in turn, can be a part of a conjugative (transferable) plasmid (11, 119, 122, 123). Such a genetic arrangement is an excellent avenue for the dissemination of these genes. The vanB cluster is often located on the host chromosome and initially was thought not to be transferable to other bacteria. However, it can also occur on plasmids, and, even when it is chromosomal, this gene cluster has been transferable as part of large mobile elements, perhaps related to large conjugative transposons (212).
(iv) VanC glycopeptide resistance.
Low-level resistance to vancomycin is typical of E. gallinarum, E. casseliflavus, and E. flavescens. The nucleotide sequences of the vanC-1 gene in E. gallinarum, the vanC-2 gene in E. casseliflavus, and the vanC-3 gene in E. flavescens have been reported, although there is some disagreement about whether E. flavescens is a legitimate enterococcal species (52). VanC ligase of E. gallinarum favors the production of a pentapeptide terminating in d-Ala–d-Ser. Substitution of d-Ser for d-Ala is presumed to weaken the binding of vancomycin to the novel pentapeptide. Insertional inactivation of vanC-1 unmasks the concomitant production of the d-Ala–d-Ala pentapeptide in E. gallinarum (216). d,d-Dipeptidase and d,d-carboxypeptidase activities analogous to those of VanA and VanB strains have been described. It is presumed that the level of resistance expressed represents the balance achieved between normal and abnormal peptidoglycan synthesis (80). The presence of variable amounts of d-Ala–d-Ala relative to d-Ala–d-Ser could account for the variable levels of vancomycin resistance observed among isolates of VRE carrying the VanC phenotype (186). That is, lower MICs could be explained by the presence of larger amounts of d-Ala–d-Ala, which enables vancomycin to inhibit cell wall synthesis, and higher MICs could be explained by a higher proportion of d-Ala–d-Ser. Resistance may be inducible or constitutive (221). The vanC-2 gene of E. casseliflavus demonstrates approximately 66% nucleotide sequence similarity to vanC-1. Like E. gallinarum, these strains also possess an additional native ligase (189). There is extensive homology (98%) between the gene sequences of vanC2 and vanC3 (52). vanA genes have recently been identified in strains of E. gallinarum and E. casseliflavus, conferring higher levels of resistance to vancomycin (MIC, >256 μg/ml) in these species than normally anticipated and also resulting in resistance to teicoplanin (68).
(v) VanD glycopeptide resistance.
A novel vancomycin resistance gene designated vanD was first described in a New York Hospital in 1991 (206). The strain carrying this resistance trait was an E. faecium strain that was inhibited by vancomycin at 64 μg/ml and teicoplanin at 4 μg/ml. Partial sequencing of the ligase gene showed that it was distinct from but similar to the vanA and vanB ligase genes. Recently, three clinical isolates of vancomycin-resistant E. faecium carrying the VanD resistance trait were found in Boston (199), and the deduced amino acid sequence of VanD showed 67% identity to those of VanA and VanB. VanD appears to be located on the chromosome and is not transferable to other enterococci.
(vi) VanE glycopeptide resistance.
The vanE vancomycin resistance gene has recently been described in E. faecalis BM4405, which is resistant to low levels of vancomycin (MIC, 16 μg/ml) and susceptible to teicoplanin (MIC, 0.5 μg/ml) (94). This new resistance phenotype has similarities to the intrinsic VanC type of resistance. The deduced amino acid sequence has a greater identity to VanC (55%) than to VanA (45%), VanB (43%), or VanD (44%) (94).
(vii) Other resistance classes and organisms.
Lactobacillus casei , Pediococcus pentosaceus, and Leuconostoc mesenteroides are naturally resistant to glycopeptides. Although the terminus appears to be the same (d-Ala–d-Lac), as found in VRE with VanA or VanB phenotypes (24, 120), DNA from these organisms does not hybridize with resistance gene probes prepared from VRE (24, 120).
In the laboratory, conjugal transfer of VanA-type vancomycin resistance genes from enterococci to other gram-positive cocci has been accomplished. Recipient organisms in successful transfers have included group A and viridans group streptococci, Listeria monocytogenes, and Staphylococcus aureus (57, 189). Transfer of resistance genes to S. aureus, resulting in high levels of resistance to vancomycin, was demonstrated both in vitro and on the skin of mice.Vancomycin-resistant Entercocci – Essay Example. This gives rise to concern that such transfer in humans under natural conditions indeed might be feasible (193). Vancomycin resistance genes have already been found in human isolates of nonenterococcal organisms. A vanB-related gene sequence (designated vanB3) has been found in Streptococcus bovis (208).
(viii) Vancomycin-dependent enterococci.
An interesting phenomenon that has developed in some strains of VanA- and VanB-type VRE is that of vancomycin dependence (64, 261). These enterococci are not just resistant to vancomycin but now require it for growth. Vancomycin-dependent enterococci have been recovered from apparently culture-negative clinical samples by plating them onto vancomycin-containing agar, such as that used for isolation of Campylobacter or gonococci. A likely explanation for the phenomenon of vancomycin dependence is that these enterococci turn off their normal production of d-Ala–d-Ala and then can grow only if a substitute dipeptide-like structure is made. With most VanA- and VanB-type enterococci, this occurs only in the presence of vancomycin, which induces the synthesis of associated dehydrogenase (VanH) and ligase (VanA or VanB) that make d-Ala–d-Lac. The reason for the cell turning off the synthesis of d-Ala–d-Ala is that as long as vancomycin is present, d-Ala–d-Ala is not necessary for cell wall synthesis by VRE (186). Indeed, it is being destroyed by the action of VanX. Once the vancomycin is removed, d-Ala–d-Lac is no longer synthesized, and without either d-Ala–d-Ala or d-Ala–d-Lac, the cell cannot continue to grow or replicate. Reversion to vancomycin independence has been observed; it probably occurs by either a mutation that leads to constitutive production of d-Ala–d-Lac or one that restores the synthesis of d-Ala–d-Ala.
EPIDEMIOLOGY AND CONTROL
Geographic Distribution and Spread within Hospitals
Since their initial recovery from patients in the United Kingdom and France, VRE have been found in many other countries, including Australia, Belgium, Canada, Denmark, Germany, Italy, Malaysia, The Netherlands, Spain, Sweden, and the United States (261).
From 1989 through 1993, the percentage of nosocomial enterococcal infections reported to the Centers for Disease Control and Prevention’s National Nosocomial Infections Surveillance system that were due to VRE increased from 0.3 to 7.9% (43). The increase was mainly due to the 34-fold rise (from 0.4 to 13.6%) of VRE infections in intensive care unit (ICU) patients, although a trend toward increased VRE infections also was noted in non-ICU patients (43).
Hospital outbreaks of infection or colonization have been reported with both VanA and VanB isolates (29). Such outbreaks may involve clonal dissemination of strains indistinguishable by pulsed-field gel electrophoresis (PFGE), not only within hospitals but also among several local hospitals (180). Multiple clones are often encountered, and sporadic isolates of unrelated strains may coexist with a predominant clone suspected of institutional spread (30, 147). In hospitals in which VRE outbreaks have been detected at an early stage, cases often have been caused by a single strain (29, 30, 51, 121, 164, 176). When VRE have been present in a hospital or community for months or years, molecular typing of isolates often reveals that vancomycin resistance has spread by plasmids or transposons to many different clones (51, 122, 167, 181, 235). Vancomycin-resistant Entercocci – Essay Example.
Patients may be colonized simultaneously with more than one strain of VRE (167, 252). Stool isolates of VRE have included a number of different species such as E. faecalis, E. faecium, E. gallinarum, E. casseliflavus, E. avium, and E. mundtii (19). Fortunately, rates of stool colonization with VRE among hospitalized patients far exceed infection rates with these organisms (147, 176). Gastrointestinal tract colonization with VRE may persist for weeks or months, and single negative cultures may be intermixed with positive cultures over time (176). During outbreaks, environmental cultures in hospital rooms have yielded VRE (29, 167, 235).
VRE in Long-Term-Care Facilities
The role of long-term-care facilities (LTCFs) in the epidemiology of VRE has not been well defined. In a study performed in Chicago, where VRE have been endemic for several years, it was found that 47% of patients admitted to a hospital from LTCFs were colonized with VRE (M. L. Elizaga, D. Beezhold, M. K. Hayden, et al., Abstract, Clin. Infect. Dis. 23:925, 1996). The prevalence of VRE among LTCF residents, however, varies considerably by geographic area (32). Several preliminary reports emphasized that 10 to 16% of patients admitted to the hospital from nursing homes were colonized with VRE (M. P. Revuelta, J. A. Nord, R. L. Yarrish, et al., Abstract, Clin. Infect. Dis. 21:730, 1995; S. J. Sargent, V. S. Baselski, L. D. Reed, et al., Abstract, Clin. Infect. Dis. 21:729, 1995). In two reports, most or all nursing-home residents who were colonized with VRE had been hospitalized in an acute-care hospital within the preceding 3 months (29; J. Quale, K. Patel, M. Zaman, et al., Abstract, Clin. Infect. Dis. 21:733, 1995). Bonilla et al. reported that VRE colonization of residents in a Veterans’ Affairs (VA) LTCF in Michigan ranged from 9% (in December 1994) to 19% (in January 1996) (27). During the same periods, 47 and 33% of residents’ rooms were contaminated with VRE, respectively. Transmission between roommates was not observed. During the surveys, it was found that 26 to 41% of health care workers carried VRE on their hands. In another recent study in a VA LTCF in Pittsburgh, vancomycin-resistant E. faecium was identified in 24 of the 36 patients at the time of transfer from an acute-care facility (35). VRE in these patients persisted for a median of 67 days after identification. Treatment of VRE colonization with antimicrobials prolonged colonization. Serial surveillance of the 34-bed ward showed that the rates of colonization were stable, with only three documented instances of VRE acquisition. The authors of this report also noted that during 2.5 years of surveillance for infection, a single case of bacteremia occurred in a patient in whom colonization with VRE could not be demonstrated by rectal swab culture and no infections occurred in patients colonized with VRE. These studies indicate that colonized residents of LTCFs may serve as a reservoir for VRE for acute-care hospitals, just as patients from acute-care hospitals may reintroduce VRE to an LTCF continually.
VRE in the Community
In the United States, attention has focused on the epidemiology of VRE mainly in hospitals, and there is little evidence to suggest that transmission of VRE to healthy adults occurs to any significant extent in the community (B. E. Murray, Editorial response, Clin. Infect. Dis. 20:1134–1136, 1995). In a study in Texas, investigators failed to find any VRE in the feces or carcasses of chickens (186; Murray, Editorial response). In addition, VRE could not be isolated from healthy volunteers in two studies (186, 252; Murray, Editorial response).Vancomycin-resistant Entercocci – Essay Example. Two cases of apparent community-acquired VRE urinary tract infections in New York City have been reported (104). In another case, the husband caregiver of an elderly woman colonized with VRE developed urinary retention and urinary tract infection with a VRE strain that was found to be indistinguishable from the woman’s isolate by PFGE (231). Thus, as colonized patients leave the hospital environment, the possibility that transmission might occur in the community cannot be discounted.
The situation in Europe is quite different from that in the United States. In Europe, VRE have been isolated from sewage and various animal sources (19, 139). It has been suggested that the use of glycopeptide-containing animal feeds in some regions of Europe may have contributed to such differences (184). In one study, VanA-resistant E. faecium was isolated from frozen poultry and pork and from the feces of 12 of 100 nonhospitalized inhabitants in a rural area (139). VanA VRE have also been found in the feces or intestines of other farm animals or pets, including horses, dogs, chickens, and pigs (65). These observations suggest a potential for VRE or the resistance genes of VRE to reach humans through the food chain or through contact with domesticated animals.
Colonization of healthy individuals with VRE does not necessarily indicate a risk of infection with these organisms. In a point-prevalence culture survey at one Belgian hospital in 1993, 3.5% of patient stool isolates were positive for VRE; however, to that point, no infections due to VRE had been encountered at that institution (111). Van der Auwera et al. reported that stool cultures from 11 (28%) of 40 healthy volunteers who were not health care workers and who had not taken antibiotics in the preceding year yielded a heterogeneous collection of isolates of vancomycin-resistant E. faecium (249). The same group also detected VRE in the stools of up to 64% of volunteers who had received oral glycopeptides in previous studies (249). Vancomycin-resistant Entercocci – Essay Example.
