CDC links antibiotic use, resistance in GISA patient
A classic case of 'use it and lose it'
A detailed case study of one of the first patients in the United States to be infected with a Staphylococcus aureus strain with intermediate resistance to vancomycin reveals a classic pattern of antimicrobial use contributing to resistance, the Centers for Disease Control and Prevention reports.
The organism was first reported in Japan, and in August of 1997 the first U.S. cases appeared in two patients infected in Michigan and New Jersey.1-3 At that time, the organism was referred to as vancomycin intermediate-resistant Staphylococcus aureus (VISA), but the CDC is now using the name GISA for glycopeptide intermediate-resistant S. aureus. A third U.S. case was reported this year in New York, and additional GISA strains have been reported in England and France.
The clinical profile of one of the U.S. cases was described at a recent CDC public health training network satellite broadcast for physicians, nurses, infection control professionals, and others interested in curbing the rise of resistant pathogens. The CDC did not identify which of the cases was the subject of the clinical profile, but it appears to correspond with other descriptions of the second U.S. case, which was reported last year by clinicians at Our Lady of Lourdes Medical Center in Camden, NJ. That patient subsequently died after the GISA infection cleared, and prolonged intermittent exposure to vancomycin and other antibiotics for methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) infections was previously described. (See Hospital Infection Control, January 1998, pp. 8-9; October 1997, pp. 145-152.)
Observing 'dramatic increase' in resistance
"Antimicrobials were once seen as medical miracles," William Jarvis, MD, chief of the investigation and prevention branch of the CDC hospital infections program, said at the training session. "We're now discovering that the more we use them, the quicker we lose them. We've seen dramatic increases in antimicrobial resistance among nosocomial pathogens on the worldwide front. The two major risk factors are antimicrobial use and noncompliance with recommended infection control practices." (See related story, p. 156.)
Key developments in the case study described at the training teleconference are summarized as follows:
· A 66-year-old male patient with congestive heart failure and diabetes mellitus was admitted to the hospital in February 1997 for an evaluation of shortness of breath. The patient was diagnosed with a urinary tract infection due to MRSA and VRE. He was treated with intravenous vancomycin at 1 g daily every 10 days and oral doxycycline at 100 mg a day for 10 days.
· Seven days into the treatment, the patient developed acute renal failure requiring peritoneal dialysis. Peritoneal fluid cultures taken at the time of catheter insertion grew MRSA. The catheter remained in place 11 days, and no further cultures were obtained.
· On day 16 of the patient's hospitalization, an MRSA bloodstream infection was diagnosed, and he received four more weeks of IV vancomycin at 1 g every three days. After two weeks of IV vancomycin, blood cultures returned negative.
· In April and July the patient again developed recurrent MRSA bloodstream infections, but no localized infections were identified, and no foreign bodies were present between each of these episodes. Bone and white blood cell scans done to assess the possible presence of occult infection also were negative. Transesophageal echocardiography revealed insignificant aortic and mitral insufficiency but no valvular vegetation. Each episode was treated with IV vancomycin, 1 g every three days. Two peak serum vancomycin levels during this time were 32.5 µg/ml and 26.4 µg/ml. Combined trough and random serum vancomycin levels ranged from 4.6 to 26.2, with the median at 16.6 µg/ml. Only one random vancomycin level, at 4.6 µg/ml, fell below the recommended serum vancomycin trough range.
· On Aug. 6, after a total of 11 weeks of vancomycin therapy, a blood culture that was supposed to determine the therapy's effectiveness grew S. aureus resistant to methicillin and intermediate-resistant to the glycopeptide vancomycin. At first, this bloodstream infection was treated on an outpatient basis with IV vancomycin, 1 g every 10 days, but on Aug. 11, IV gentamicin at 80 mg every day was added when a glycopeptide intermediate-resistant S. aureus (GISA) isolate was discovered.
· The patient then developed pedal and pulmonary edema on Aug. 26. Oral rifampin at 300 mg a day was added. Two days later, the patient was admitted to the hospital for rapidly progressive renal insufficiency, which was thought to be secondary to his nephrotoxic medications, and peritoneal dialysis was begun. After four weeks of antimicrobial therapy for the GISA infection, all antimicrobials were discontinued.
· On Sept. 23, the patient's temperature rose to 100.4°F, and blood cultures grew Candida species. Peritoneal fluid cultures grew Staphylococcus epidermidis and urine cultures grew Pseudomonas species. No GISA was isolated from these cultures.
· Despite being treated with IV amphotericin B, 45 mg per day, plus oral doxycycline, 100 mg twice a day, and ciprofloxacin, 500 mg every 12 hours, the patient died 34 days after the final hospitalization.
'The link of use to resistance is undeniable'
The clinical details in the GISA case reveal a clear pattern of use and subsequent resistance in a severely ill patient, faculty members at the training session emphasized.
"This is a classic example of antimicrobial use leading to the evolution of further antimicrobial resistance in the infecting strain," Jarvis said. "This patient received vancomycin for 18 of the 23 weeks for MRSA and VRE before diagnosis of the GISA infection. Previous in vitro studies have shown that if bacteria are exposed to low levels of an antimicrobial, they can develop resistance to that agent."
John McGowan Jr., MD, professor of epidemiology and medicine at Emory University in Atlanta, added, "I think that's right. The link of use to resistance is undeniable, and the setting is right for this: a severely ill patient with compromised host defenses."
References
1. Centers for Disease Control and Prevention. Staphylococcus aureus with reduced susceptibility to Vancomycin - United States, 1997. MMWR 1997; 46: 765-766.
2. Centers for Disease Control and Prevention. Update: Staphylococcus aureus with reduced susceptibility to vancomycin - United States, 1997. MMWR 1997; 46: 813-814.
3. Centers for Disease Control and Prevention. Reduced susceptibility of Staphylococcus aureus to vancomycin - Japan, 1996. MMWR 1997; 46:624-626.
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