Infections are major cause of hospitalization and death in the dialysis and transplant populations, and treatment of these infections could be made more challenging by the emergence of pathogens resistant to multiple antimicrobial agents.
“We have observed trends of increasing antimicrobial resistance among Gram-negative bloodstream isolates, particularly Escherichia coli isolates, in kidney and other solid organ transplant recipients,” said Majdi N. Al-Hasan, MD, an infectious disease specialist now with the Division of Infectious Diseases at the University of Kentucky in Lexington.
He and his colleagues studied the incidence and outcomes of Gram-negative bloodstream infections among solid organ transplant recipients receiving care at Mayo Clinic in Rochester, Minn. From 1996 to 2007, antimicrobial resistance rates among E. coli bloodstream isolates in solid organ transplant recipients increased from 50% to 75% for ampicillin and 0% to 44% for ciprofloxacin.
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“In kidney transplant recipients, antimicrobial resistance rates of E. coli bloodstream isolates increased from 40% to 74% for ampicillin and from 0% to 53% for ciprofloxacin during the same period,” Dr. Al-Hasan said.
From 2000 to 2007, the prevalence of E. coli bloodstream isolates producing extended spectrum beta-lactamases increased from 0 to 11% in kidney transplant recipients, he said.
The results appear in the American Journal of Transplantation (2009;9:835-843).
In a separate study of Pseudomonas aeruginosa bloodstream infections conducted at the University of Pittsburgh Medical Center, researchers found that transplant recipients are at greater risk for multidrug-resistant P. aeruginosa bloodstream infections than non-transplant patients, according to paper published in Transplant Infectious Disease (2009;11:227-234).
Over a 10-year period, researchers studied 503 subjects, 149 of them transplant recipients. Of the P. aeruginosa blood culture isolates from transplant recipients, 43% were multidrug resistant compared with 18% of isolates from non-transplant recipients.
MRSA
In the dialysis population, researchers have observed an emerging problem with methicillin-resistant Staphylococcus aureus (MRSA). From 1995 to 2002, the percentage of dialysis centers treating one or more patients with MRSA rose from 40% to 76%, according to a report in Seminars in Dialysis (2005;18:52-61).
The incidence of invasive MRSA infections among dialysis patients in 2005 was 45.2 cases per 1,000 population, indicating a 100-fold greater risk for these infections compared with the general population, according to the Centers for Disease Control and Prevention (CDC). Of 5,287 cases of invasive MRSA reported to the CDC by the Active Bacterial Core surveillance system during 2005, 813 (15.4%) were in dialysis patients.
Furthermore, in a study by investigators at St. John Hospital and Medical Center in Detroit, 40 (33%) of 120 hospitalized dialysis patients had S. aureus nasal colonization. Of these 40, 26 (65%) were colonized with MRSA, according to data published in Infection Control and Hospital Epidemiology (2009;30:4-8). Infections developed in eight of these 26 patients, whereas only one infection developed in 14 patients colonized with methicillin-susceptible S. aureus, which the researchers said underscores the significance of MRSA nasal colonization.
Vancomycin resistance
One of the major concerns regarding MRSA is the possible development of strains that also are resistant to vancomycin, an antibiotic widely used in dialysis centers, said Loren G. Miller, MD, MPH, Associate Professor of Medicine at the David Geffen School of Medicine at the University of California in Los Angeles (UCLA) and Director of Infection Control at Harbor-UCLA Medical Center in Torrance, Calif. Few good therapeutic options are available for vancomycin-resistant S. aureus (VRSA).
Possible alternatives include linezolid, daptomycin, and telavancin (which recently received FDA approval), he said. He added that there is no evidence showing that these agents would be any more effective than vancomycin. In addition, the dosing of these agents for dialysis patients have not been fully worked out, he said.
So far, only a handful of VRSA cases have been reported, “but there are probably a lot more that haven’t been recognized because VRSA is frequently not picked up by routine microbiology laboratory methods,” said Dr. Miller, an investigator at Los Angeles BioMedical Research Institute.
For reasons that are not clear, most VRSA cases have been detected only in the Detroit area, “and they don’t seem to be epidemiologically linked to each other,” Dr. Miller said.
Nephrologists also should be alert for vancomycin intermediate resistant S. aureus (VISA) infections, he said. They should suspect VISA or VRSA infections in patients who are not responding as expected to vancomycin treatment, Dr. Miller said.
In addition, vancomycin-resistant enterococcal infections could be on the increase in dialysis patients, he said. “This can be a challenge to treat because the number of drugs that can treat these infections is limited.”
The possibility of drug-resistant infections in dialysis patients has implications for empiric treatment, Dr. Miller noted. Most infections in HD patients are caused by Gram-positive organisms (mostly S. aureus), Dr. Miller explained. Clinicians should consider the possible presence of Gram-negative pathogens in patients who are not responding to empiric treatment with drugs (such as vancomycin) that are only active against Gram-positive organisms. At Harbor-UCLA, typical empiric therapy for bloodstream infections in HD patients is vancomycin plus a drug active against Gram-negative bacteria, such as ceftazidime, he said.
Meanwhile, bloodstream infections and cellulitis seem to be on the rise among dialysis patients, mostly likely because of prolonged use of vascular-access catheters. Having a catheter is very large risk factor for having a bloodstream infection,” Dr. Miller said.
