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Biomedical subjects

Franklin D Lowy

Publications and source records attributed to Franklin D Lowy.

18 recordsLinked to original sources

Heterosexual transmission of community-associated methicillin-resistant Staphylococcus aureus.

Heterosexual transmission of community-associated methicillin-resistant Staphylococcus aureus has not been documented. As part of a survey conducted in northern Manhattan, we encountered 3 households in which heterosexual transmission was responsible for new community-associated methicillin-resistant S. aureus infection. The vaginal and inguinal isolates obtained from the sexual partners were USA 300. This report documents an important and previously unrecognized means of community-associated methicillin-resistant S. aureus colonization and transmission for these potentially invasive strains.

Adult↗

The role of Staphylococcus aureus adhesins in the pathogenesis of ventricular assist device-related infections.

Ventricular assist devices (VADs) are an important form of therapy for end-stage congestive heart failure. However, infection of the VAD, which is often caused by Staphylococcus aureus, poses a major threat to survival. Using a novel in vitro binding assay with VAD membranes and a heterologous lactococcal system of expression, we identify 3 S. aureus proteins--clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as the main factors involved in adherence to VAD polyurethane membranes. Adherence is greatly diminished by long implantation times, reflecting a change in topological features of the VAD membrane, and is primarily mediated by the FnBPA domains in the staphylococcal proteins. We also compare the adherence of S. aureus mutant strains and show that other staphylococcal components appear to be involved in adherence to VAD membranes. Finally, we demonstrate that ClfA, FnBPA, and FnBPB mediate bacterial infection of implanted murine intra-aortic polyurethane patches.

Adhesins, Bacterial↗

Effectiveness of barrier precautions and surveillance cultures to control transmission of multidrug-resistant organisms: a systematic review of the literature.

BACKGROUND: Despite the priority placed on preventing transmission of multidrug-resistant organisms (MDROs) in health care facilities, there is a lack of consensus among recommended infection control guidelines. We focused on control measures that have a great potential to affect patient care, patient services, and hospital cost/resources: barrier precautions/patient isolation and surveillance cultures. METHODS: We conducted a systematic review of the literature and published English-language guidelines pertaining to the use of barrier precautions/patient isolation and surveillance cultures to prevent the transmission of MDROs. The recommendations made by the published guidelines were summarized and compared. The primary research studies identified through our literature search were evaluated for study quality. We then summarized the outcomes of the studies with the highest quality scores and made recommendations for future work. RESULTS: A total of 29 studies were included in our assessment of study quality; of those, 7 studies were of high quality. CONCLUSION: This systematic review identified key gaps in the literature including a need for greater monitoring of implementation of the interventions, more cost analyses of interventions, determining the independent contribution of specific interventions, and identifying the minimum interventions needed to reduce transmission.

Bacteria↗

Meticillin-resistant Staphylococcus aureus among US prisoners and military personnel: review and recommendations for future studies.

We reviewed published work examining the prevalence and risk factors for meticillin-resistant Staphylococcus aureus (MRSA) infection in two high-risk groups: prisoners and military enlistees. Significant risk factors for infection included prison occupation, gender, comorbidities, prior skin infection, and previous antibiotic use. Although characteristics such as hygiene, physical contact, and crowding were postulated as risk factors for MRSA infection, there were few epidemiological studies supporting these factors. Most studies identified were retrospective in design and only one study used prospective surveillance for MRSA colonisation among all individuals residing within a single military setting. Our results suggest that there is a high incidence of MRSA infection among individuals in prisons and military settings, but surveys that quantify the prevalence of MRSA colonisation among individuals living within these specialised settings are needed. A thorough examination of MRSA acquisition and transmission patterns in prisons and military settings could help elucidate preventive strategies in other crowded and closed settings.

Female↗

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.

Cardiac Output, Low↗

Antimicrobial-resistant bacteria in the community setting.

Over the past decade, antimicrobial resistance has emerged as a major public-health crisis. Common bacterial pathogens in the community such as Streptococcus pneumoniae have become progressively more resistant to traditional antibiotics. Salmonella strains are beginning to show resistance to crucial fluoroquinolone drugs. Community outbreaks caused by a resistant form of Staphylococcus aureus, known as community-associated meticillin (formerly methicillin)-resistant Staphylococcus aureus, have caused serious morbidity and even deaths in previously healthy children and adults. To decrease the spread of such antimicrobial-resistant pathogens in the community, a greater understanding of their means of emergence and survival is needed.

Adult↗

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.

Acquired Immunodeficiency Syndrome↗

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.

Adult↗

Staphylococcus aureus colonization and the risk of infection in critically ill patients.

OBJECTIVE: To evaluate the relationship between Staphylococcus aureus nasal and tracheal colonization and infection in medical intensive care unit (MICU) patients. The primary outcome was the incidence of S. aureus infection in colonized versus non-colonized patients. DESIGN: Prospective, observational cohort study. Patients admitted to the MICU during the study period were screened for S. aureus nasal and tracheal colonization by culture and a PCR assay twice weekly. Demographic, clinical, and microbiologic data were collected in the MICU and for 30 days after discharge. PFGE and antibiotic susceptibility testing were performed on all S. aureus nasal, tracheal, and clinical isolates. RESULTS: Twenty-three percent of patients (47 of 208) were nasally colonized with S. aureus. Twenty-four percent of these patients developed S. aureus infections versus 2% of non-colonized patients (P < .01). Nine of 11 patients with both nasal colonization and infection were infected by their colonizing strain. Two of 47 nasally colonized patients developed an infection with a different strain of S. aureus. Fifty-three percent of intubated patients with nasal colonization (10 of 19) had tracheal colonization with S. aureus as opposed to 4.9% of intubated, non-colonized patients (3 of 61) (P < .01). Parenteral antibiotics were ineffective at clearing nasal colonization. PCR detected S. aureus colonization (nasal and tracheal) within 6.5 hours with a sensitivity of 83% and a specificity of 99%. CONCLUSIONS: The incidence of S. aureus infection was significantly elevated in nasally colonized MICU patients. Techniques to rapidly detect colonization in this population may make targeted topical prevention strategies feasible.

Anti-Bacterial Agents↗

Report of the National Heart, Lung and Blood Institute-National Institute of Allergy and Infectious Diseases working group on antimicrobial strategies and cardiothoracic surgery.

Infections related to cardiac surgery increase morbidity and mortality, and increase cost and use of health resources. With the widespread use of synthetic materials, whether in prosthetic valves or vascular conduits, bacterial infection and, more rarely, fungal complications can be devastating, requiring prolonged antimicrobial therapy and, at times, re-operations with high morbidity and mortality rates. With the US population aging and living longer, cardiac surgery is applied to an older population with significant comorbidities, making the threat from infectious complications significant. The dwindling armamentarium of existing antimicrobial agents, a limited pharmaceutical pipeline of future therapies, and the emergence of antimicrobial-resistant bacteria have increased the challenge of treating cardiothoracic infections. Thus, there is critical need for addressing the existing and emerging issues in this area to develop new safe and effective strategies to address the clinical challenges facing cardiothoracic surgeons. As a result of this need, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases convened a Working Group on April 4 and 5, 2002, in Bethesda, Md, which explored both basic science and clinical research opportunities in the prevention and treatment of major infections after cardiac surgery. Because of its importance as the most common pathogen in this setting, the focus of discussions was on the prevention and treatment of Staphylococcus aureus infections. This report summarizes the 5 main areas that the Working Group targeted (epidemiology of infections, molecular mechanisms of infections and complications, current pharmacotherapy, new frontiers, and clinical trial design) and highlights the recommendations that were set forth by the Working Group.

Antibiotic Prophylaxis↗

Antimicrobial strategies for the prevention and treatment of cardiovascular infections.

As prosthetic cardiovascular devices become more common, the risk of complicating infections increases. The confluence of high-risk procedures, prosthetic material and antibiotic-resistant bacteria has made the management of these cardiovascular infections a challenge. A limited number of new antimicrobial agents have been introduced with activity against the resistant gram-positive organisms that are responsible for such problematic cardiovascular infections. Among these are the new agents quinupristin/dalfopristin and linezolid. In addition, several new therapeutic agents (e.g. daptomycin, lysostaphin and a Staphylococcus aureus vaccine) are in varying stages of clinical trials. Other strategies, such as the use of synergistic antibiotic combinations, the prophylactic eradication of bacterial colonization and the exploration of agents specifically targeting bacterial biofilms, are potentially valuable methods that are currently under investigation.

Anti-Bacterial Agents↗

Strains of Staphylococcus aureus obtained from drug-use networks are closely linked.

Drug users have a higher incidence of colonization with Staphylococcus aureus than does the general population, and, as a result, they are at increased risk of infection with their colonizing strain. The purpose of this study was to examine the role of drug-use risk networks in S. aureus transmission, the similarity of S. aureus isolates within these networks, and the possible role of inhalation drug use paraphernalia in the transmission of S. aureus. Strains of S. aureus are shared among colonized inhalation drug users within drug-use risk networks. It suggests that patterns of drug use and the geographic location where drug sharing occurs are major contributors to the transfer of staphylococci and, as a result, to the high prevalence of staphylococcal colonization and perhaps disease in this population.

Adult↗

New methods to investigate infectious disease transmission and pathogenesis--Staphylococcus aureus disease in drug users.

Staphylococcus aureus is the single most important bacterial pathogen in infections among drug users. It is responsible for several diseases, ranging from superficial cutaneous abscesses to life-threatening intravascular infections. Although the nature of these infections is well described in published work, there is limited understanding of their epidemiology and pathogenesis. This limitation is in part due to the difficulty of studying disease transmission among drug users in the community, and the limitations of the investigative tools that have so far been used. We review the current understanding of the pathogenesis of staphylococcal disease in drug users and argue for the integration of molecular epidemiological techniques and social network methodology to increase our understanding of the basis for the persistence, distribution, and transmission dynamics of S aureus among drug users. Finally, we propose a framework for investigating the transmission of pathogens in community-based settings.

HIV Infections↗

Differences between Staphylococcus aureus isolates from medical and nonmedical hospital personnel.

It is unclear whether the levels of Staphylococcus aureus colonization of hospital personnel with patient exposure are increased or whether personnel become colonized with more antibiotic-resistant strains. Differences in nasal and hand carriage of S. aureus between medical and nonmedical hospital personnel were examined. No differences in nasal carriage between the two groups were found; however, there was a trend that suggested differences in the rates of hand carriage of S. aureus (18% of nonmedical personnel and 10% of medical personnel). Medical personnel were colonized with more antibiotic-resistant isolates than nonmedical personnel (mean, 2.8 versus 2.1 isolates [P < 0.03]), and the strain profiles indicated that they tended to be more clonal in origin, suggesting that exposure to hospital isolates alters the colonization profile.

Adult↗