ATLANTA Since the 1980s, when methicillin-resistant Staphylococcus aureus (MRSA) first emerged in the United States, vancomycin had been the last effective antimicrobial available for treating serious S. aureus infections. But two reported cases of vancomycin-resistant S. aureus in Michigan and New Jersey within one month has doctors concerned that full vancomycin resistance may have finally arrived on the scene.
Widespread use of antimicrobials is being blamed for the vancomyin resistant organisms. These episodes emphasize the need to enhance laboratory capacity at the hospital and state levels to recognize these strains, the importance of prudence in using antibiotics and the requirement for full implementation of recommended infection-control measures to prevent transmission of these strains.
"We are concerned," said William Jarvis, MD, acting director of the Hospital Infections Program at the Centers for Disease Control and Prevention's (CDC) National Center for Infectious Diseases. "Vancomycin is the last effective agent for treating serious infections. There are no other effective drugs left."
The first isolate immediately resistant to vancomycin (NSA) in the United States was reported in a Michigan resident. VISA-associated peritonitis was diagnosed in patients being treated with with long-term ambulatory peritoneal dialysis. During January-June the patient had been treated with multiple courses of vancomycin for repeated episodes of vancomycin-susceptible, MRSA associated peritonitis. Although intermediately resistant to vancomycin, the VISA isolate was susceptible to chloramphenicol, rifampin, trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline. The patient continued to receive antimicrobial therapy at home. Cultures were obtained from the hands and nares of the patient's household contacts, hospital roommates, health care workers but, none of these cultures were positive for VISA.
The following month, a VISA-associated bloodstream infection was diagnosed in a New Jersey resident with long-term MRSA colonization and repeated MRSA infections since February. Since February, the patient has had vancomycin resistant enterococcal (VRE) colonization. During the months of March through August, the patient had been treated with multiple courses of vancomycin for repeated MRSA bloodstream infections. In August, a blood culture from the patient grew an MRSA strain with intermediate resistance to vancomycin all previous MRSA strains had been susceptible to vancomycin.
The isolate was susceptible to gentamicin, TMP-SMX, tetracycline and imipenem. The patient continued to receive antimicrobial therapy at home.
The first MRSA case occurred in May 1996, when a 4-month-old boy developed a nosocomial surgical-site infection in a hospital in Japan. He received treatment with vancomycin for a month, but fever and surgical site purulent discharge continued, and the C-reactive protein (CRP) remained elevated. Treatment was changed to a combination of vancomycin and arbekacin; the purulent discharge subsided after 12 days. However, after the therapy was stopped, the child's fever and surgical inflammation reoccurred, subcutaneous abscesses were detected, and the CRP increased to 3.5 mg/dL. Arbekacin, was resumed in combination with ampicillin and sulbactam. His fever subsided and the CRP declined below detectable levels after a week. After débridement of the subcutaneous abscesses and therapy with arbekacin and ampicillin and sulbactam for an additional two weeks, the child improved. Antimicrobial therapy was stopped and he was discharged from the hospital.
The MRSA strain isolated from the purulent discharge and from the debridement sample demonstrated a vancomycin minimum inhibitory concentration (MIC) of 8 mg/mL.
"In the pre-antibiotic era, S. aureus were a common cause of death among the world's populations," said Jarvis. "Although the availability of penicillin in 1944 offered an important advance in the treatment of the infection it was relatively short-lived."
Resistance was first recognized in 1944 and was caused by production of a penecillinase enzyme capable of deactivating penicillin, by the late 1950s, said Jarvis, about half of strains were resistant to penicillin. These strains were associated with widespread outbreaks before the development of semisynthetic penicillinase-resistant agents in 1960; however, resistance to methicillin was reported as early as 1965 in England. In the U.S., the proportion of MRSA isolates reported increased from just 2% in 1975 to 35% last year. In Japan, analysis of approximately 7,000 strains isolated from patients in various geographic areas during 1992 and 1993 indicate that 60% of S. aureus isolates were resistant to methicillin.
"Decreasing the likelihood of further emergence of vancomycin-resistant strains here in the United States depends, in part, on actions taken now to prevent the spread of these strains in health-care facilities, including prudent vancomycin use and infection-control measures such as health care worker hand washing," said Jarvis.
Steps for Handling Organisms with Reduced Vancomycin Susceptibility
To prevent the spread of staphylococci with reduced susceptibility to vancomycin within and among facilities and to minimize the potential for the organism to become endemic, take the following steps:
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