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Volume 340:493-501 February 18, 1999 Number 7 Next

Abstract PDF Editorial by Waldvogel, F. A. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Since the emergence of methicillin-resistant Staphylococcus aureus, the glycopeptide vancomycin has been the only uniformly effective treatment for staphylococcal infections. In 1997, two infections due to S. aureus with reduced susceptibility to vancomycin were identified in the United States.

Methods We investigated the two patients with infections due to S. aureus with intermediate resistance to glycopeptides, as defined by a minimal inhibitory concentration of vancomycin of 8 to 16 µg per milliliter. To assess the carriage and transmission of these strains of S. aureus, we cultured samples from the patients and their contacts and evaluated the isolates.

Results The first patient was a 59-year-old man in Michigan with diabetes mellitus and chronic renal failure. Peritonitis due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus peritonitis associated with dialysis. The removal of the peritoneal catheter plus treatment with rifampin and trimethoprim–sulfamethoxazole eradicated the infection. The second patient was a 66-year-old man with diabetes in New Jersey. A bloodstream infection due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus bacteremia. This infection was eradicated with vancomycin, gentamicin, and rifampin. Both patients died. The glycopeptide-intermediate S. aureus isolates differed by two bands on pulsed-field gel electrophoresis. On electron microscopy, the isolates from the infected patients had thicker extracellular matrixes than control methicillin-resistant S. aureus isolates. No carriage was documented among 177 contacts of the two patients.

Conclusions The emergence of S. aureus with intermediate resistance to glycopeptides emphasizes the importance of the prudent use of antibiotics, the laboratory capacity to identify resistant strains, and the use of infection-control precautions to prevent transmission.

Since the emergence of methicillin-resistant S. aureus, the glycopeptide vancomycin has been the only uniformly effective treatment for staphylococcal infections. The recent emergence of glycopeptide resistance in coagulase-negative staphylococci has heightened concern about whether S. aureus could acquire glycopeptide resistance^{5,6,7,8,9,10,11,12}; the emergence of such resistance could produce morbidity and mortality similar to that caused by S. aureus infections in the era before antibiotics became available.

In May 1996, the world's first documented clinical infection due to S. aureus with intermediate resistance to glycopeptides (glycopeptide-intermediate S. aureus) was diagnosed in a patient in Japan.^13,14 In this report, we describe our investigation of the first documented glycopeptide-intermediate S. aureus infections in the United States and discuss the clinical significance and public health implications of the emergence of these organisms.

Methods

Definition, Ascertainment, and Review of Cases

An S. aureus isolate with intermediate resistance to glycopeptides was defined as an S. aureus isolate associated with a minimal inhibitory concentration of vancomycin of 8 to 16 µg per milliliter.¹⁵ A patient who had an infection caused by glycopeptide-intermediate S. aureus at William Beaumont Hospital, Royal Oak, Michigan, or Our Lady of Lourdes Hospital, Camden, New Jersey, from August 1996 to August 1997 was considered a case patient.

To identify S. aureus isolates with intermediate resistance to glycopeptides, we reviewed the hospitals' laboratory records to identify any S. aureus isolate associated with a minimal inhibitory concentration of vancomycin that was 4 µg per milliliter or higher for retesting. For each patient who had an infection with S. aureus with intermediate resistance, we reviewed the available medical records to obtain information on the clinical course and outcome, any antecedent use of antimicrobial agents, therapy, and contacts with health care personnel. These patients were interviewed to determine their activities and details of their recent medical care.

Infection-Control Policies and Practices

Next, we reviewed infection-control policies and practices at facilities and agencies where patients found to have resistant isolates had received care. To assess infection-control practices, we administered a standardized questionnaire to personnel who had provided direct care to the patients with resistant infection. We asked them about their knowledge of the patient's infection or carriage status, and their use of barrier precautions (e.g., gloves, gown, and mask) when caring for the infected patients.

Investigation of Contacts

To assess potential transmission of S. aureus with intermediate resistance to glycopeptides, we identified the hospital roommates, health care providers, and household contacts of patients with resistant isolates and cultured specimens from their hands and nares.

Laboratory Methods

Glycopeptide-intermediate S. aureus and epidemiologically related S. aureus isolates were sent to the Centers for Disease Control and Prevention (CDC) for confirmation of the species by standard reference methods¹⁶ and for antimicrobial-susceptibility testing with broth-microdilution methods.¹⁷ Isolates of S. aureus with intermediate resistance to glycopeptides were typed by pulsed-field gel electrophoresis.^17,18

S. aureus isolates with intermediate glycopeptide resistance were examined by scanning and transmission electron microscopy. For scanning electron microscopy, modifications of standard scanning electron microscopical techniques¹⁹ were used to fix, embed, and stain the organisms, which were then observed with a Philips XL20 scanning electron microscope (Philips Electronic Instruments, Mahwah, N.J.). To obtain transmission electron micrographs, modifications of standard transmission electron microscopy techniques²⁰ were used to fix, embed, and stain the organisms, which were then observed with a Philips 410 TEM transmission electron microscope (Philips Electronic Instruments).

Specimens for culture were obtained by swabbing the anterior nares with a dry sterile swab and were inoculated onto mannitol salt agar and incubated at 35°C. Specimens for culture from the hands were obtained by the wipe–rinse technique.²¹ Rinse fluid obtained with the wipe–rinse technique was passed through a 0.45-µm membrane filter (Advantec MFS, Pleasanton, Calif.). The filters were then implanted on Columbia nutrient agar (Becton Dickinson Microbiology Systems, Cockeysville, Md.) and mannitol salt agar. The cultures of specimens from the hands were incubated for up to seven days at 35°C. Isolates were screened by the Staphaurex Rapid latex test (Murex Diagnostics, Norcross, Ga.) and the coagulase tests.¹⁶ All S. aureus isolates were tested for susceptibility to vancomycin by agar-plate dilution.²² In Michigan, cultures of specimens from the hands and nares of the patient and contacts were transported to the Michigan Department of Community Health for identification of the species and testing for susceptibility to vancomycin. All specimens from New Jersey were sent directly to the CDC.

Case Reports

Patient 1

Patient 1 was a 59-year-old man in Michigan who had diabetes mellitus, hypertension, metastatic small-cell carcinoma of unknown primary origin, and chronic renal failure that had required continuous ambulatory peritoneal dialysis since 1992. In February 1997, he was given a diagnosis, as an outpatient, of peritonitis after nausea and vomiting developed (Figure 1). The peritoneal-fluid cell count was 790 white cells per deciliter, of which 88 percent were polymorphonuclear leukocytes. Gram's staining of the peritoneal fluid revealed gram-positive cocci, and cultures grew methicillin-resistant S. aureus. The patient was treated with intravenous vancomycin (1 g every 72 hours) for 14 days. The indwelling peritoneal catheter had no insertion-site inflammation and was not removed. Cultures of peritoneal fluid obtained after the completion of intravenous vancomycin therapy were negative. Over the subsequent five months, the patient had four additional episodes of culture-confirmed methicillin-resistant S. aureus peritonitis; each was treated with intravenous vancomycin, predominantly on an outpatient basis. The patient received vancomycin for a total of 18 weeks before glycopeptide-intermediate S. aureus was identified; peak serum levels of vancomycin (median, 33 µg per milliliter; range, 20.6 to 42.3) and trough levels (median, 10.4 µg per milliliter; range, 6.2 to 19.7) were within recommended limits.²³

View larger version (11K): [in this window] [in a new window]   Figure 1. Time Line Showing the Clinical Course of Patients 1 and 2. Dark bands show the duration of therapy or symptoms, plus signs the presence of symptoms or abnormalities or positive test results, and minus signs negative test results. GPC denotes gram-positive cocci, MRSA methicillin-resistant Staphylococcus aureus, and GISA glycopeptide-intermediate S. aureus.

 
On July 19, 1997, S. aureus with intermediate glycopeptide resistance was cultured from the patient's peritoneal fluid. Antimicrobial agents to which the isolate was susceptible included chloramphenicol, rifampin, trimethoprim–sulfamethoxazole, and tetracycline. Initially, the patient was treated as an outpatient with intravenous vancomycin (1 g every 72 hours) and intramuscular tobramycin (120 mg every 5 days). However, he continued to have abdominal pain and was hospitalized. Vancomycin was administered intraperitoneally at a dosage of 50 mg per 2 liters of dialysate twice a day and intravenously at 1 g every 72 hours. Cultures of peritoneal fluid obtained on days 12 and 19 of vancomycin therapy remained positive for S. aureus with intermediate glycopeptide resistance. On August 18, oral rifampin (300 mg daily) was added to the patient's regimen. On August 21, oral trimethoprim–sulfamethoxazole (160 mg and 800 mg daily) was also added; vancomycin and gentamicin were discontinued. At the time of our investigation, 23 days after the initiation of therapy, S. aureus was cultured from the patient's hands; no S. aureus with intermediate glycopeptide resistance was detected.

On September 5, 49 days after antimicrobial therapy for glycopeptide-intermediate S. aureus was begun, peritoneal-fluid cultures became negative; the peritoneal catheter was removed 4 days later. Culture of material from the catheter revealed no S. aureus. The patient had received a total of 16 days of rifampin and trimethoprim–sulfamethoxazole and was discharged on hemodialysis. The patient resumed continuous ambulatory peritoneal dialysis with no recurrence of peritonitis.

Surveillance cultures of specimens from the axilla, nares, vascular catheters, and peritoneal catheters were performed until January 6, 1998, and remained negative for S. aureus with intermediate glycopeptide resistance. The patient died at home, under hospice care. No autopsy was performed.

Patient 2

Patient 2 was a 66-year-old man in New Jersey who had congestive heart failure and diabetes mellitus; he was admitted to the hospital on February 4, 1997, for evaluation of shortness of breath. A urinary tract infection due to methicillin-resistant S. aureus and vancomycin-resistant enterococci was diagnosed; the patient was treated with intravenous vancomycin (1 g on day 1) and oral doxycyline (100 mg daily for 10 days). Seven days into treatment, acute renal failure developed that required peritoneal dialysis. Cultures of peritoneal fluid obtained at the time of catheter insertion grew methicillin-resistant S. aureus. After 11 days, when dialysis was no longer required, the peritoneal catheter was removed, and no further peritoneal fluid for culture was obtained. On day 16 of hospitalization, a methicillin-resistant S. aureus bloodstream infection was diagnosed, and the patient received intravenous vancomycin (1 g every three days) for four more weeks. Blood cultures were negative after two weeks of intravenous vancomycin.

In April and July, the patient had three recurrences of methicillin-resistant S. aureus bloodstream infection; no localized infections were identified, and no foreign bodies were present at the time each infection was diagnosed. Bone scanning and white-cell scanning to detect possible occult infection were also negative. Transesophageal echocardiography showed clinically insignificant aortic and mitral insufficiency, but no valvular vegetations. Each episode was treated with intravenous vancomycin (1 g every three days). The peak serum vancomycin levels measured on two occasions were 32.5 µg per milliliter and 26.4 µg per milliliter. Trough levels and randomly measured serum vancomycin levels ranged from 4.6 to 26.2 µg per milliliter (median, 16.6). Only one randomly measured vancomycin level (4.6 µg per milliliter) fell below the recommended range for the trough serum level of vancomycin.²³

On August 6, 1997, after a total of 18 weeks of vancomycin therapy, a culture of blood drawn to evaluate the response to therapy grew S. aureus with intermediate resistance to glycopeptides. The bloodstream infection was initially treated on an outpatient basis with intravenous vancomycin (1 g every 10 days). On August 11, after the S. aureus isolate was recognized as having intermediate resistance to vancomycin, intravenous gentamicin (80 mg per day) was added. At the time of our investigation, four days after the addition of gentamicin, no S. aureus was cultured from specimens obtained from the patient's hands or nares.

On August 26, pedal and pulmonary edema developed, and oral rifampin (300 mg daily) was added to the patient's regimen. Two days later, he was admitted to the hospital for rapidly progressive renal insufficiency, thought to be due to his nephrotoxic medications, and peritoneal dialysis was begun. After four weeks of antimicrobial therapy for S. aureus infection with intermediate resistance to glycopeptides, all antimicrobial drugs were discontinued. On September 23, his temperature was 38.0°C (100.4°F), and blood cultures grew Candida glabrata and C. parapsilosis; peritoneal-fluid cultures grew S. epidermidis; urine cultures grew klebsiella and pseudomonas species. No S. aureus with intermediate resistance to glycopeptides was isolated from these cultures. Despite treatment with intravenous amphotericin B (45 mg per day) and oral doxycycline (100 mg twice a day) and ciprofloxacin (500 mg every 12 hours), the patient died 34 days after admission. Consent for an autopsy was refused.

Results

Infection-Control Policies and Practices

While infected with S. aureus with intermediate resistance to glycopeptide, these two patients received care at three hospitals and affiliated outpatient clinics, at five physicians' offices, and through two home health agencies. Each of these medical care settings had written infection-control policies that were consistent with the CDC's recommended precautions for the care of patients infected with antimicrobial-resistant pathogens. In Michigan, contact isolation precautions (i.e., private rooms, gowns, gloves, and use of antimicrobial soap) were used for Patient 1 on his admission to the hospital because of his carriage of methicillin-resistant S. aureus; while he was receiving outpatient care in physicians' offices and hospital clinics and at home, standard precautions were generally used. In New Jersey, Patient 2 was also placed on contact isolation precautions at the time of hospitalization, because of a prior infection with vancomycin-resistant enterococci.

Among the 151 health care workers who provided direct care to these patients, 62 (41 percent) knew the patients were colonized or infected with methicillin-resistant S. aureus or vancomycin-resistant enterococci, and 118 (78 percent) used gloves, with or without further barrier methods, when delivering care to the patients.

Investigation of Contacts

We identified 235 contacts (79 in Michigan and 156 in New Jersey); 58 hospital employees (25 percent) were unavailable because of vacations (33 workers) or hospital policy (25 workers). The remaining 177 contacts (54 in Michigan and 123 in New Jersey) were 86 nurses or nurse's assistants, 23 physicians, 15 home health aides, 11 phlebotomists, 10 household contacts, 8 hospital roommates, 7 technicians, 4 orderlies, 4 emergency-response personnel, 3 physical therapists, 3 medical students, 2 hospital chaplains, and 1 dietitian. All agreed to provide material for culture. Sixty (34 percent) of these contacts (21 in Michigan and 39 in New Jersey) were positive for S. aureus; 10 (17 percent) had hand carriage only, 40 (67 percent) had nares carriage only, and 10 (17 percent) had both. No carriage of S. aureus with intermediate resistance to glycopeptides was found.

Results of Laboratory Tests

According to broth-microdilution methods, the isolates of S. aureus with intermediate resistance to glycopeptides from both patients had minimal inhibitory concentrations of 8 µg per milliliter of vancomycin both on initial testing and after passage through 20 subcultures. In contrast, on disk-diffusion testing, the Michigan and New Jersey isolates were read as susceptible to vancomycin at 18 and 17 mm, respectively. Both isolates were resistant to penicillin, oxacillin, ciprofloxacin, erythromycin, and clindamycin, but both remained susceptible to chloramphenicol, dalfopristin, quinupristin, tetracycline, and trimethoprim–sulfamethoxazole. Patient 1's isolate was resistant to gentamicin and teicoplanin and susceptible to rifampin, whereas Patient 2's isolate was resistant to rifampin and susceptible to gentamicin and teicoplanin.¹⁷ With the exception of intermediate resistance to vancomycin, the susceptibility patterns of the S. aureus isolates were similar to those of each patient's previous strain of methicillin-resistant S. aureus. Population analysis confirmed the presence of glycopeptide-intermediate subpopulations of S. aureus.

Pulsed-field gel electrophoresis revealed a difference of two bands between the two S. aureus isolates with intermediate resistance to glycopeptides (Figure 2). Patient 1's glycopeptide-intermediate S. aureus isolate and a methicillin-resistant S. aureus isolate from the patient's hands had indistinguishable patterns on pulsed-field gel electrophoresis (Figure 2). No methicillin-resistant S. aureus isolate from Patient 2 was available for comparison.

View larger version (97K): [in this window] [in a new window]   Figure 2. Patterns of SmaI-Digested DNA of S. aureus Isolates on Pulsed-Field Gel Electrophoresis. S denotes lambda molecular-size standards; lane 1, S. aureus American Type Culture Collection 29213 control; lane 2, a methicillin-resistant S. aureus isolate from Georgia; lane 3, a glycopeptide-intermediate S. aureus isolate from Patient 1 in Michigan; lane 4, a methicillin-resistant S. aureus isolate from Patient 1 in Michigan; and lane 5, a glycopeptide-intermediate S. aureus isolate from Patient 2 in New Jersey.

 
Scanning and transmission electron microscopy showed a layer of extracellular material of unknown chemical composition in the S. aureus isolates with intermediate resistance to vancomycin that was thicker than that in the methicillin-resistant S. aureus control isolates (Figure 3A, Figure 3B, Figure 3C, Figure 3D, Figure 3E, and Figure 3F).

View larger version (517K): [in this window] [in a new window]   Figure 3. Electron Micrographs of S. aureus Isolates. The top row shows scanning electron micrographs magnified 50,000 times; the bottom row, transmission electron micrographs magnified 348,000 times. Panels A and D show a glycopeptide-intermediate S. aureus isolate from Patient 1 in Michigan, in which increased extracellular material is evident; Panels B and E, methicillin-resistant S. aureus from Georgia, showing a normal cell wall without increased extracellular material; and Panels C and F, a glycopeptide-intermediate S. aureus isolate from Patient 2 in New Jersey, with evidence of increased extracellular material.

 
Discussion

We investigated the first two documented infections with S. aureus with intermediate resistance to glycopeptides in the United States. To date, a total of four glycopeptide-intermediate S. aureus infections have been documented worldwide,¹³ the first in Japan and, more recently, the fourth in New York. The emergence of S. aureus with intermediate glycopeptide resistance raises a number of questions: Who is at risk for infection with these strains of S. aureus? Are these strains clinically important? What is the mechanism of resistance? Finally, how can infection with S. aureus with intermediate resistance to glycopeptides be prevented and controlled?

Although the small number of documented infections due to glycopeptide-intermediate S. aureus precludes a formal risk assessment, there are certain common features among the four documented cases. First, all four patients had prior infections with methicillin-resistant S. aureus, for which they received repeated and prolonged vancomycin therapy. Second, three of the four received long-term or temporary dialysis. Third, three of the four had poor clinical response to vancomycin therapy. These findings suggest that monitoring for colonization or infection with S. aureus with intermediate glycopeptide resistance may be warranted among patients who are often treated with vancomycin, such as patients on dialysis.

The clinical course of the patients infected with S. aureus with intermediate vancomycin resistance suggests that even partial glycopeptide resistance among S. aureus is clinically important. Eradication of the glycopeptide-intermediate S. aureus infection in the patient in Japan required surgical débridement and prolonged therapy with ampicillin–sulbactam and arbekacin, an aminoglycoside unavailable in the United States.¹⁴ The first U.S. patient required seven weeks of combination antimicrobial therapy and removal of a peritoneal catheter for successful eradication of the infection. The second U.S. patient also required prolonged antimicrobial therapy, which was complicated by impaired renal function that required continuous ambulatory peritoneal dialysis. S. aureus with intermediate glycopeptide resistance should be suspected in any patient in whom otherwise appropriate vancomycin therapy for S. aureus infection appears to be ineffective.

Recently advocated approaches to the treatment of infections include the treatment of abscesses without drainage²⁴ and the use of vancomycin without surveillance of serum vancomycin levels.²⁵ Although these approaches may prove successful in some cases, the recent experience with infections caused by S. aureus with intermediate glycopeptide resistance suggests that abscesses must be drained and that adequate antimicrobial levels must be maintained for therapy to be successful.^{23,26,27,28,29}

Options for the treatment of infections caused by S. aureus with intermediate glycopeptide resistance should be based on the organism's antimicrobial-susceptibility profile. An expanded antimicrobial-susceptibility profile may be necessary, depending on the laboratory's standard susceptibility panel. Some patients with S. aureus infection also benefit from consultation with an infectious-disease specialist.²⁹ Fortunately, to date all S. aureus isolates with intermediate glycopeptide resistance have been susceptible to alternative agents, including newly developed agents.¹⁷

Glycopeptide resistance may have emerged in S. aureus because of interspecies transfer of resistance genes or selection of resistant mutants as a result of prolonged antimicrobial therapy. The ability of gram-positive organisms to acquire glycopeptide-resistance genes became a matter of concern with the emergence of vancomycin-resistant enterococci, and vancomycin-resistance genes have been transferred from vancomycin-resistant enterococci to S. aureus in vitro.⁶ However, none of the S. aureus isolates with intermediate glycopeptide resistance have had vanA, vanB, vanC1, vanC2, or vanC3 genes,¹⁷ suggesting that interspecies transfer of resistant genes from vancomycin-resistant enterococci³⁰ is not the mechanism by which glycopeptide resistance developed in these S. aureus isolates.

Certain common factors in the cases of the two U.S. patients suggest that cellular modification due to prolonged vancomycin exposure was probably responsible for the emergence of glycopeptide resistance in these isolates. Both patients had received multiple prolonged courses of vancomycin for methicillin-resistant S. aureus infections. The patients' methicillin-resistant S. aureus isolates and their S. aureus isolates with intermediate glycopeptide resistance had similar minimal inhibitory concentrations of antimicrobials other than vancomycin. In addition, S. aureus isolates that had intermediate vancomycin resistance had increased extracellular material associated with the cell wall — a finding similar to that observed in S. aureus organisms with intermediate glycopeptide resistance induced in vitro.^7,31,32 The thickened extracellular material has been shown to sequester vancomycin⁷ and to reduce the susceptibility of S. aureus to vancomycin.³² Although the exact mechanism of vancomycin resistance has not been determined, these data suggest that it emerged through the selection of naturally occurring resistant mutants during prolonged exposure to vancomycin. Elucidation of these mechanisms will be essential for the development of effective therapeutic agents.

The two S. aureus isolates with intermediate resistance to glycopeptides that were isolated from U.S. patients had similar patterns on pulsed-field gel electrophoresis. The S. aureus isolates with intermediate glycopeptide resistance and the colonizing methicillin-resistant S. aureus isolates from one patient were indistinguishable, suggesting that the methicillin-resistant S. aureus isolate may have been the progenitor of the S. aureus with intermediate glycopeptide resistance. The apparent similarity between the two geographically distant and epidemiologically unrelated isolates from the patients in Michigan and New Jersey probably reflects our inability to distinguish the genetic ancestry of the methicillin-resistant S. aureus isolates in the United States because of the limited number of strains. The two S. aureus isolates with intermediate glycopeptide resistance in the U.S. patients differed from the Japanese isolate.¹⁷

The widespread use of vancomycin and other antimicrobial agents that resulted in the dramatic increase in the prevalence of vancomycin-resistant enterococci in U.S. hospitals³³ may cause a similar increase in the prevalence of S. aureus with intermediate glycopeptide resistance. Data from Japan show that methicillin-resistant S. aureus with heteroresistance to vancomycin (heteroresistance is the manifestation of the resistance phenotype by only small subpopulations of the strain) is present in a number of hospitals.¹⁴ The prevalence of heteroresistant methicillin-resistant S. aureus isolates in U.S. hospitals is unknown. Fortunately, each of the hospitals to which the U.S. patients were admitted had infection-control policies in place for patients with antimicrobial-resistant infections or colonization, and we documented no carriage of S. aureus with intermediate glycopeptide resistance among the household or medical contacts of either patient. The lack of transmission of these resistant S. aureus infections suggests that adherence to recommended infection-control practices may prevent the transmission of S. aureus with intermediate glycopeptide resistance from patient to patient and from patient to health care worker. Nevertheless, continuing education of clinicians about the indications for vancomycin use is needed to reduce the overuse and misuse of vancomycin and other antimicrobial agents in all health care settings, including inpatient and outpatient facilities (such as dialysis units). The development of innovative intervention programs, such as clinical practice guidelines and "antibiotic stop orders," which lead to automatic discontinuation of a prescribed antimicrobial agent after a predetermined interval, may increase compliance with the recommendations of the Hospital Infection Control Practices Advisory Committee and reduce overall use of antimicrobials (Table 1).²²

View this table: [in this window] [in a new window]   Table 1. Situations in Which the Use of Vancomycin Should Be Discouraged.

 
Recently, the CDC issued specific recommendations intended to reduce the development and transmission of S. aureus with intermediate glycopeptide resistance (Table 2). First, laboratory personnel should use a quantitative method based on the minimal inhibitory concentration to detect S. aureus isolates with intermediate glycopeptide resistance. Vancomycin disk diffusion does not reliably identify S. aureus isolates with decreased susceptibility to glycopeptides.¹⁷ Second, programs to educate health care personnel about infection-control precautions against S. aureus with intermediate glycopeptide resistance should be developed, and infection-control specialists should monitor compliance with these precautions. Third, infection-control and laboratory personnel should implement active surveillance for S. aureus with intermediate glycopeptide resistance, particularly in populations at high risk, such as patients on dialysis and patients in whom vancomycin therapy is unsuccessful.¹⁷ If an S. aureus isolate with potential intermediate resistance to glycopeptides is identified, prompt notification of the state health department and the CDC is critical so that epidemiologic and laboratory support can be provided.

View this table: [in this window] [in a new window]   Table 2. Recommendations for Preventing the Spread of Glycopeptide-Resistant Staphylococci.

 
The emergence of S. aureus with intermediate glycopeptide resistance threatens to return us to the era before the development of antibiotics. To prevent further emergence of S. aureus strains with intermediate glycopeptide resistance and the emergence of S. aureus with full vancomycin resistance, the use of vancomycin must be optimized, laboratory methods for the detection of resistant pathogens must be enhanced, and infection-control precautions must be strictly followed for infected or colonized patients.

The use of company or trade names is for identification only and does not imply endorsement by the Public Health Service or the Department of Health and Human Services.

We are indebted to Lori Boschetto, B.S.N., Catherine Crain, M.T., B.S.N., and Sandy Pine, B.S., Our Lady of Lourdes Medical Center, Camden, N.J.; Gary Burke, D.O., Haddon Cardiology Associates, Haddon Heights, N.J.; Colin Campbell, D.V.M., and Herman Ellis, M.D., New Jersey Department of Health and Senior Services, Trenton; Gael Rodgers, R.N., B.S.N., Bon Secours of Michigan Healthcare System, Grosse Pointe; and James Sunstrum, M.D., Oakwood Hospital, Dearborn, Mich., for their invaluable contributions to our investigation.

^* Other members of the Glycopeptide-Intermediate Staphylococcus aureus Working Group are listed in the Appendix.

Source Information

From the Hospital Infections Program (T.L.S., M.L.P., M.V.L., F.C.T., W.R.J.) and the Division of Viral and Rickettsial Disease (E.W.), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta; the Michigan Department of Community Health, Lansing (K.R.W., B.R.-D.); and William Beaumont Hospital, Royal Oak, Mich. (C.C., M.J.Z., J.D.B.).

Address reprint requests to Dr. Pearson at the Hospital Infections Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd., NE, MS E-69, Atlanta, GA 30333.

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In addition to the authors, the members of the Glycopeptide-Intermediate Staphylococcus aureus Working Group were as follows: M.J. Arduino, J.H. Carr, N. Clark, B. Hill, S. McAllister, and J.M. Miller, Hospital Infections Program, National Center for Infectious Diseases, CDC, Atlanta; and G. Jennings, Michigan Department of Community Health, Lansing.

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