multidrug-resistant enterococci: the dawn of a new era in - NCBI

MULTIDRUG-RESISTANT ENTEROCOCCI: THE DAWN OF A NEW ERA IN RESISTANT PATHOGENS Suresh J. Antony, MD El Paso, Texas

Resistant enterococci, especially vancomycin-resistant enterococci, have rapidly become an important nosocomial pathogen. They are increasingly prevalent among hospitalized patients, patients with serious chronic illnesses, and immunosuppressed patients. Risk factors identified include previous antibiotics, exposure to contaminated equipment, and close proximity to infected patients. Treatment of multidrug-resistant pathogens has become increasingly difficult, with increased morbidity and mortality in these patients. Strict infection control measures remain the mainstay in the management of these infections. (J Nat! Med Assoc. 1 998;90:537-540.)

Key words: enterococci * multidrug resistance

Enterococci increasingly are being recognized as important nosocomial pathogens and are the second most frequent cause of nosocomial infections after Escherichia coli. In addition, the changing epidemiology of nosocomial infections suggests that the number of infections caused by this organism will continue to increase with increasing mortality and morbidity. Nosocomial vancomycin-resistant enterococci infections have increased from 0.3% in 1989 to 13.6% in 1993.1 Two species of enterococci, Enterococcusfaecalis and Enterococcusfaeciun, which reside in the gastrointestinal and genitourinary tract, account for the majority of clinical infections including bacteremia and endocarditis. Due to their intrinsic resistance to several antimicrobials, including vancomycin, these infections have become increasingly difficult to eradicate and treat. This article examines the changing epidemiology, pathogenesis, resistance, and treatment modalities of this infection. From Texas Oncology PA and Texas Tech University Medical Center, El Paso, Texas. Requests for reprints should be addressed to Dr Suresh J. Antony, Texas Oncology PA, El Paso Cancer Treatment Ctr, 7848 Gateway Blvd E, El Paso, TX 79915. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 90, NO. 9

CLINICAL MANIFESTATIONS Enterococci cause a wide spectrum of infections ranging from soft-tissue infections to bacteremia, urinary tract infection, and abdominopelvic infections. Pneumonia and endocarditis caused by these pathogens increasingly have been reported.2'3 In a prospective, observational study of 110 patients with serious infections due to Enterococcus spp in six university and community teaching hospitals in Connecticut, it was noted that serious community and nosocomial enterococcal infections involved a variety of sites with antibiotic resistance being commonly noted.3 Infections included cardiovascular, 54% (catheter-related bacteremia, 28%; primary bacteremia, 18%; endocarditis, 6%; and septic thrombophlebitis, 1%); intra-abdominal, 13% (including cholangitis and renal); skin and soft tissue, 5%; bone and joint, 4%; pleuropulmonary, 4%; central nervous system, 3%; deep surgical wound, 3%; and endometritis, 2%. Enterococcusfaecium was responsible for 20% of all infections, with E faecalis being responsible for the remaining 80% of infections.2

Endocarditis Enterococci are the third most common cause of infective endocarditis, exceeded only by Staphyl537

MULTIDRUG-RESISTANT ENTEROCOCCI

ococcus spp and Streptococcus viridans.4'5 Most patients with endocarditis have an underlying valvular disorder, most often involving aortic and mitral valves. Tricuspid valve involvement has not been documented. The source of the infecting organism is usually the genitourinary tract and also may be a result of infection following surgery or instrumentation of the genitourinary tract.6

Enterococcal Bacteremia Eight percent of all cases of bacteremia in the United States are caused by enterococci.7'8 The most common sources of enterococci are the genitourinary tract, the intra-abdominal system, and skin and soft-tissue sites, including intravenous access lines.

Urinary Tract Infecfion Enterococci are the second leading cause (after E of nosocomial urinary tract infection and account for 16% of such infections.2'3 Patients with structural abnormality, patients who have undergone urinary tract instrumentation, and elderly men with prostate problems often are affected. Pregnant women with enterococcal colonization of the vagina may be the source of neonatal sepsis in up to 13% of cases of neonatal sepsis.

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Intra-Abdominal and Pelvic Infection Enterococci have been isolated in up to 25% of intra-abdominal and pelvic infections, which are usually of the mixed type.9 The pathogenic role of enterococci in this setting is controversial as antimicrobial agents that have no activity against enterococci have seemingly cured intra-abdominal infections. On the other hand, breakthrough enterococcal bacteremia has been reported in patients with intra-abdominal or pelvic infection who are receiving antibiotics that do not have in vitro activity against enterococci.10"11 From a clinical perspective, enterococci do not routinely call for treatment in intra-abdominal and pelvic infections, except in biliary tree infections and when the organism is specifically isolated.'2"3

Skin and Soft-Tissue Infection Enterococci are not known to cause primary cellulitis but are found in previously devitalized tissue and have been isolated from burns, diabetic foot ulcers, decubitus ulcers, and abdominal surgery wounds. Their pathogenicity in this setting is supported by the relatively high incidence of bacteremia arising from skin and soft-tissue sites. 538

RISK FACTORS Many studies have tried to define the risk factors for developing antibiotic-resistant enterococci infection, especially vancomycin-reistant enterococci. These include prior use of antibiotics such as vancomycin, aminoglycosides, cephalosporins, and metronidazole.14 In addition, the greater the number of antibiotic days, the higher the risk of colonization and infection. Other risk factors, such as having renal insufficiency, undergoing invasive procedures, being present in chronic care medical wards and nursing homes, and having an underlying immunodeficiency (such as being a transplant recipient or having cancer) are predisposing factors to the development of these infections.0-v Human immunodeficiency virus infection does not appear to be a risk factor. Finally, the longer the hospitalization, the higher the risk of acquiring the infections, either from another patient or from an infected health-care worker.1819 The mortality of patients with vancomycin-sensitive organisms is 17% and 36% for vancomycin-resistant organisms.Y

RESISTANCE Despite the recent availability of many new classes of antimicrobial agents, enterococci continue to pose a therapeutic problem. This is due to the intrinsic resistance of this pathogen to several antimicro-

bials including cephalosporins, aminoglycosides, penicillin, metronidazole, and vancomycin.L5,',20 In addition, many drugs of choice such as penicillin and vancomycin are not bactericidal unless combined with an aminoglycoside. This problem is probably due to the widespread indiscriminate use of broadspectrum antibiotics that lack enterococcal activity and the acquisition of new mechanisms of antibiotic resistance.21-23 Such recently acquired resistance to high-level aminoglycoside resistance eliminates synergistic killing with combination therapy.'9'24 Some success has been reported with various combinations of cell wall active agents, but no prospective comparative studies are available.25'26 In addition, other new mechanisms of resistance including beta-lactamase production, vancomycin resistance, and high-level ampicillin resistance are increasing in prevalence.27'28 Most recently, reports of vancomycin-resistant enterococcal infections have been increasing in the literature. Resistance due to this infection is mainly plasmid-mediated. There is no effective cure for this infection.'

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PREVENTION AND CONTROL As there is no effective treatment for such resistant infections, institutions must ensure that a preventive program is in place for such infections. A multidisciplinary approach is essential for the prevention and control of resistant enterococcal infections. These include educational programs to emphasize the epidemiology of resistant enterococci and to stress the importance of appropriate infection control measures necessary to prevent the spread of this bacteria.'4'29'30 Some of the principals of infection control for enterococci infection include the recognition that these organisms are easily transmissible from person to person, person to environment, and vise versa. In addition, it has the capacity for prolonged survival on environmental surfaces. Therefore, it is essential that all personnel wear gloves and possibly gowns on entering the room of a colonized or infected patient.31'32 Handwashing with an antibacterial soap before and after contact should be mandatory.33'34 The segregation of staff and patients so that personnel do not contaminate noncolonized patients also is helpful.35'36 Maintenance of effective cleaning policies should be reviewed regularly and enforced.

TREATMENT The treatment of patients with such isolates of enterococci has become increasingly difficult and in some instances impossible to treat. This is of particular importance in patients with vancomycin-resistant enterococci infections and high-level aminoglycoside-resistant strains.25'30'37'38 In vitro susceptibility studies of vancomycin-resistant enterococci have shown that many isolates are susceptible to novobiocin, chloramphenicol, and nitrofurantoin, and these drugs have been used to treat some individuals with isolates susceptible to these agents with variable results.30'38 A new investigational injectable streptogramin antibiotic (quinupristin/dalfopristin) has been used to treat patients with such infections. However, the success rate with this drug has not been spectacular. Other drugs such as investigational fluoroquinolonestrovofloxacin, cinafloxacin, and sparfloxacin, and teichoplanin have been used with varying degrees of success. The treatment of high-level aminoglycoide-resistant enterococci infections also have posed a problem. Some investigators have used a combination of vancomycin, imipenem, and ampicillin with a resultJOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 90, NO. 9

ing clinical cure, but prospective studies on this regimen are not available as yet.25'26'39 Although it is uncertain how vancomycin-resistant enterococci will affect the hospital environment in the next decade, the increased prevalence of this emerging nosocomial pathogen has created considerable concern. Because currently available treatment regimens are less than optimal, each institution needs to develop a comprehensive strategic plan. In addition, an infectious disease consultation, especially in patients with severe infections such as endocarditis and bacteremia would be useftil. The Centers for Disease Control and Prevention (CDC)/Hospital Infection Control Practices Advisory Committee (HICPAC) have made recommendations on the use of vancomycin, and many institutions have adapated these recomendations with success. In addition, routine screening for vancomycin-resistant isolates as well as early detection and rigorous infection control measures also should reduce the risk of future epidemics and prevent unnecessary morbidity and mortality.

CONCLUSION The age of multidrug-resistant enterococci has arrived and with it comes the realization that the treatment of such infections are difficult or almost impossible. Therefore, preventive measures such as those described above are vitally important in the management of these infections. Physicians should resist the urge to use vancomycin and other broadspectrum antimicrobials purely for the convenience of dosing. Finally, when such infections do occur, it would be prudent to obtain the advice of an infectious disease specialist.

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