Rachel J. Gordon

Pathogenesis of Methicillin-Resistant Staphylococcus aureus Infection

Staphylococcus aureus is a versatile pathogen capable of causing a wide range of human diseases. However, the role of different virulence factors in the development of staphylococcal infections remains incompletely understood. Some clonal types are well equipped to cause disease across the globe, whereas others are facile at causing disease among community members. In this review, general aspects of staphylococcal pathogenesis are addressed, with emphasis on methicillin-resistant strains. Although methicillin-resistant S. aureus (MRSA) strains are not necessarily more virulent than methicillin-sensitive S. aureus strains, some MRSA strains contain factors or genetic backgrounds that may enhance their virulence or may enable them to cause particular clinical syndromes. We examine these pathogenic factors.

Ventricular assist device-related infections

Heart failure is a leading cause of death in developed nations despite medical management. Cardiac transplantation is a potentially lifesaving intervention for approximately 4000 advanced heart failure patients per year; however, the demand for donor hearts far exceeds the supply. Ventricular assist devices provide temporary support for patients with severe heart failure until myocardial recovery occurs or a donor heart becomes available. For those ineligible for transplantation, ventricular assist devices may be used permanently and have demonstrated reduced mortality and an improved quality of life compared with continued medical therapy. Nonetheless, these devices are under-used, in part due to the frequency of complications. Device-related infections are one of the most frequent sequelae of ventricular assist device placement and occur in 18-59% of cases. Infections can involve any part of the device and confer substantial morbidity and mortality. Here, we provide an introduction to ventricular assist devices, explore the nature and pathogenesis of ventricular assist device-related infections, discuss problems with diagnosis, and present treatment and prevention strategies.

Prospective, Multicenter Study of Ventricular Assist Device Infections

Background— Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections. Methods and Results— One hundred fifty patients scheduled for VAD implantation were enrolled (2006–2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073–0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001). Conclusions— This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

The Clonality of Staphylococcus aureus Nasal Carriage

Nasal carriage of Staphylococcus aureus is often a prelude to infection with the same strain. The prevailing assumption has been that colonized individuals carry a single strain. The present study investigated the frequency of simultaneous nasal carriage of multiple strains of S. aureus. Three bacterial colonies from plated samples from colonized subjects were initially compared by pulsed-field gel electrophoresis. Fourteen of 148 S. aureus-positive samples demonstrated at least a difference of a single band; 7 of these 14 samples contained different strains, and 3 of these 7 also belonged to different accessory gene regulator (agr) types. The remaining 7 samples contained clonally related isolates; 3 of these 7 contained pairs that differed by the presence or absence of the staphylococcal chromosomal cassette mec type IV. A mathematical model that we developed predicted that approximately 6.6% of S. aureus-colonized individuals carry >1 strain. The present study demonstrates that carriage of discordant S. aureus strains in individuals with nasal colonization occurs regularly and suggests that the nares are likely sites for horizontal genetic exchange among strains.

Effect of left ventricular assist device infection on post-transplant outcomes.

BACKGROUND In this study, we sought to confirm which types of device-related infections impact bridge-to-transplant rates. We also aimed to determine the effect of device-related infections on post-transplant survival and post-transplant infection. METHODS We retrospectively reviewed paper and electronic medical records for 149 patients undergoing left ventricular assist device (LVAD) implantation as a bridge to transplantation at the Columbia Presbyterian Medical Center between 2000 and 2006. The primary outcome measures were survival to transplantation, post-transplant infection and post-transplant survival. RESULTS Patients with sepsis were less likely to be successfully bridged to cardiac transplantation (7 of 22 vs 103 of 127, 31.8% vs 81.1%, p = 0.01). However, if transplanted, their survival rates at 1 year were not decreased (6 of 7 vs 85 of 103, 85.7% vs 82.5%, p = 1.00). No other pre-transplant device-related infection affected post-transplant survival at 1 year (22 of 27 vs 69 of 83, 81.5% vs 83.1%, p = 1.00). Pre-transplant drive-line infections predicted post-transplant infection in former drive-line or pocket sites (11 of 16 vs 14 of 94, 68.8% vs 14.9%, p = 0.01) and increased overall post-transplant hospital length of stay (16 vs 19 days, p = 0.04). They did not, however, affect post-transplant survival at 1 year (22 of 25 vs 69 of 85, 88% vs 81.2%, p = 0.56). CONCLUSIONS Although survival to transplantation was diminished in LVAD patients with sepsis, if successfully transplanted, post-transplant survival was unaffected. Patients with local device infections and signs of early sepsis may warrant evaluation for urgent transplantation. A pre-transplant drive-line infection was associated with post-transplant infection in either the former pocket or drive-line site, and increased overall length of stay, but it did not decrease post-transplant survival.

A Molecular Epidemiological Analysis of 2 Staphylococcus aureus Clonal Types Colonizing and Infecting Patients with AIDS

BACKGROUND Persons with acquired immune deficiency syndrome (AIDS) who use drugs appear to be at increased risk for colonization and infection with Staphylococcus aureus. Little is known about the nature of and risk factors responsible for this association. This study is among the first to prospectively follow carriage and infection in this uniquely high-risk population. METHODS We prospectively followed the cases of 75 patients with AIDS in a residential drug treatment facility and screened for S. aureus nasal colonization and infection. RESULTS Thirty-seven baseline cultures (49%) were positive for S. aureus, and 81% of subjects were colonized at least once during the study. Thirteen subjects experienced 17 infections. Pulsed-field gel electrophoresis and sequence-based typing methods revealed that 244 (92%) of the isolates belonged to either clonal type A or B. Clonal type A was methicillin-susceptible. Clonal type B consisted of 3 main subtypes (B1, B2, and B3), all with the same allelic profile (ST8) and staphylococcal protein A gene (spa) type (7). Of note, subtype B1 was methicillin-susceptible (ST8 and spa type 7), lacking mecA, whereas the other B clones were methicillin-resistant. Both clones were resistant to trimethoprim-sulfamethoxazole. Clonal type B isolates were relatively resistant, suggesting prior exposure to the health care setting. CONCLUSIONS This study demonstrates a sustained high rate of S. aureus carriage and infection. It demonstrates the capacity of unique methicillin-resistant S. aureus clones with an established linkage to earlier outbreaks of methicillin-resistant S. aureus, as well as to human immunodeficiency virus--infected subjects, to persist in this residential setting. It also illustrates the apparent genetic instability or transmissibility of the staphylococcal chromosomal cassette mec type IV element.

Staphylococcus epidermidis Colonization Is Highly Clonal Across US Cardiac Centers

BACKGROUND Little is known about the clonality of Staphylococcus epidermidis in the United States, although it is the predominant pathogen in infections involving prosthetic materials, including ventricular assist devices (VADs). METHODS Seventy-five VAD recipients at 4 geographically diverse US cardiac centers were prospectively followed up to 1 year of VAD support. The anterior nares, sternum, and (future) driveline exit site were cultured for S. epidermidis before VAD insertion and at 7 times after surgery. Infection isolates were also collected. Isolates were typed by pulsed-field gel electrophoresis. A subset underwent susceptibility testing and staphylococcal chromosomal cassette mec and multilocus sequence typing. RESULTS A total of 1559 cultures yielded 565 S. epidermidis isolates; 254 of 548 typed isolates (46%) belonged to 1 of 7 clonal types as defined by pulsed-field gel electrophoresis. These clones were identified in up to 27 people distributed across all 4 cardiac centers. They caused 3 of 6 VAD-related infections. Disseminated clones were more antibiotic resistant than were less prevalent isolates (eg, 79% vs 54% methicillin resistant; P = .0021). CONCLUSIONS This study revealed that healthcare-associated S. epidermidis infection is remarkably clonal. We describe S. epidermidis clones that are highly resistant to antibiotics distributed across US cardiac centers. These clones may have determinants that enhance transmissibility, persistence, or invasiveness. Clinical Trials Registration. NCT01471795.

The NOSE Study (Nasal Ointment for Staphylococcus aureus Eradication): A Randomized Controlled Trial of Monthly Mupirocin in HIV-Infected Individuals

Background:HIV-positive patients at HELP/PSI, Inc, an in-patient drug rehabilitation center, had a high baseline prevalence of Staphylococcus aureus colonization (49%) and incidence of infection (17%) in a previous year-long study. Methods:A randomized, double-blinded, placebo-controlled study was conducted to determine whether repeated nasal application of mupirocin ointment would decrease the odds of S. aureus nasal colonization in 100 HELP/PSI patients over an 8-month period. A 5-day course of study drug was given monthly, and colonization was assessed at baseline and 1 month after each treatment. S. aureus infection was a secondary outcome. Results:In repeated-measures analysis, mupirocin reduced the odds of monthly S. aureus nasal colonization by 83% compared with placebo [adjusted odds ratio (ORadj) = 0.17; P < 0.0001]. Subjects colonized at study entry had a 91% reduction in subsequent colonization (ORadj = 0.09; P < 0.0001). Mupirocin also suppressed S. aureus colonization in subjects not colonized at baseline (ORadj = 0.23; P = 0.006). There was no difference in infection rates between the mupirocin and placebo groups (hazard ratio = 0.49, P = 0.29). Conclusions:Monthly application of nasal mupirocin significantly decreased S. aureus colonization in HIV patients in residential drug rehabilitation. Monthly mupirocin application has a potential role in long-term care settings or in HIV-positive patients with high rates of S. aureus colonization and infection.