Nosocomial Bloodstream Infections in US Hospitals: Analysis of 24,179 Cases from a Prospective Nationwide Surveillance Study
TL;DR: The proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals, and in neutropenic patients, infections with Candida species, enterococci, and viridans group streptococci were significantly more common.
Abstract: Background. Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality in the United States. Methods. Data from a nationwide, concurrent surveillance study (Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE]) were used to examine the secular trends in the epidemiology and microbiology of nosocomial BSIs. Results. Our study detected 24,179 cases of nosocomial BSI in 49 US hospitals over a 7-year period from March 1995 through September 2002 (60 cases per 10,000 hospital admissions). Eighty-seven percent of BSIs were monomicrobial. Gram-positive organisms caused 65% of these BSIs, gram-negative organisms caused 25%, and fungi caused 9.5%. The crude mortality rate was 27%. The most-common organisms causing BSIs were coagulasenegative staphylococci (CoNS) (31% of isolates), Staphylococcus aureus (20%), enterococci (9%), and Candida species (9%). The mean interval between admission and infection was 13 days for infection with Escherichia coli, 16 days for S. aureus, 22 days for Candida species and Klebsiella species, 23 days for enterococci, and 26 days for Acinetobacter species. CoNS, Pseudomonas species, Enterobacter species, Serratia species, and Acinetobacter species were more likely to cause infections in patients in intensive care units ( ). In neutropenic patients, infections P ! .001 with Candida species, enterococci, and viridans group streptococci were significantly more common. The proportion of S. aureus isolates with methicillin resistance increased from 22% in 1995 to 57% in 2001 ( , trend P ! .001 analysis). Vancomycin resistance was seen in 2% of Enterococcus faecalis isolates and in 60% of Enterococcus faecium isolates. Conclusion. In this study, one of the largest multicenter studies performed to date, we found that the proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals.
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Tufts Medical Center1, University of California, San Diego2, Boston Children's Hospital3, University of California, Los Angeles4, Los Angeles Biomedical Research Institute5, Providence Portland Medical Center6, Case Western Reserve University7, United States Department of Veterans Affairs8, University of Virginia9, Johns Hopkins University School of Medicine10
TL;DR: An update on potentially effective antibacterial drugs in the late-stage development pipeline is provided, in the hope of encouraging collaboration between industry, academia, the National Institutes of Health, the Food and Drug Administration, and the Centers for Disease Control and Prevention work productively together.
Abstract: The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews,” and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
4,256 citations
Cites background from "Nosocomial Bloodstream Infections i..."
...Consistently identified as the third most frequent cause of nosocomial bloodstream infection (BSI) in the United States, enterococcal BSIs remain a significant problem [48, 49]....
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TL;DR: Invasive MRSA infection affects certain populations disproportionately and is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.
Abstract: ContextAs the epidemiology of infections with methicillin-resistant Staphylococcus aureus (MRSA) changes, accurate information on the scope and magnitude of MRSA infections in the US population is needed.ObjectivesTo describe the incidence and distribution of invasive MRSA disease in 9 US communities and to estimate the burden of invasive MRSA infections in the United States in 2005.Design and SettingActive, population-based surveillance for invasive MRSA in 9 sites participating in the Active Bacterial Core surveillance (ABCs)/Emerging Infections Program Network from July 2004 through December 2005. Reports of MRSA were investigated and classified as either health care–associated (either hospital-onset or community-onset) or community-associated (patients without established health care risk factors for MRSA).Main Outcome MeasuresIncidence rates and estimated number of invasive MRSA infections and in-hospital deaths among patients with MRSA in the United States in 2005; interval estimates of incidence excluding 1 site that appeared to be an outlier with the highest incidence; molecular characterization of infecting strains.ResultsThere were 8987 observed cases of invasive MRSA reported during the surveillance period. Most MRSA infections were health care–associated: 5250 (58.4%) were community-onset infections, 2389 (26.6%) were hospital-onset infections; 1234 (13.7%) were community-associated infections, and 114 (1.3%) could not be classified. In 2005, the standardized incidence rate of invasive MRSA was 31.8 per 100 000 (interval estimate, 24.4-35.2). Incidence rates were highest among persons 65 years and older (127.7 per 100 000; interval estimate, 92.6-156.9), blacks (66.5 per 100 000; interval estimate, 43.5-63.1), and males (37.5 per 100 000; interval estimate, 26.8-39.5). There were 1598 in-hospital deaths among patients with MRSA infection during the surveillance period. In 2005, the standardized mortality rate was 6.3 per 100 000 (interval estimate, 3.3-7.5). Molecular testing identified strains historically associated with community-associated disease outbreaks recovered from cultures in both hospital-onset and community-onset health care–associated infections in all surveillance areas.ConclusionsInvasive MRSA infection affects certain populations disproportionately. It is a major public health problem primarily related to health care but no longer confined to intensive care units, acute care hospitals, or any health care institution.
3,803 citations
Cites background from "Nosocomial Bloodstream Infections i..."
...In hospitalized patients, MRSA has been a problem since the 1960s(19); approximately 20% of bloodstream infections in the hospital setting have been caused by S aureus.(20) The proportion of hospital-onset S aureus infections that were methicillin-resistant reached 64....
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...Although more recently there has been increased surveillance activity for invasive MRSA infections in the community, surveillance for MRSA bloodstream infections in the United States traditionally has been limited to hospital-onset (ie, nosocomial) disease.(20,21) As the epidemiology of MRSA disease changes, including both community- and health care–associated disease, accurate information on the scope and magnitude of the burden of MRSA disease in the US population is needed to set priorities for prevention and control....
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TL;DR: Improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy and improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.
Abstract: Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in the United States. We examined data from the National Center for Health Statistics and reviewed recent literature in order to update the epidemiology of IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per 100,000 population, since 1997, while mortality associated with invasive aspergillosis has continued to decline. Candida albicans remains the predominant cause of IC, accounting for over half of all cases, but Candida glabrata has emerged as the second most common cause of IC in the United States, and several less common Candida species may be emerging, some of which can exhibit resistance to triazoles and/or amphotericin B. Crude and attributable rates of mortality due to IC remain unacceptably high and unchanged for the past 2 decades. Nonpharmacologic preventive strategies should be emphasized, including hand hygiene; appropriate use, placement, and care of central venous catheters; and prudent use of antimicrobial therapy. Given that delays in appropriate antifungal therapy are associated with increased mortality, improved use of early empirical, preemptive, and prophylactic therapies should also help reduce IC-associated mortality. Several studies have now identified important variables that can be used to predict risk of IC and to help guide preventive strategies such as antifungal prophylaxis and early empirical therapy. However, improved non-culture-based diagnostics are needed to expand the potential for preemptive (or early directed) therapy. Further research to improve diagnostic, preventive, and therapeutic strategies is necessary to reduce the considerable morbidity and mortality associated with IC.
3,723 citations
Cites background from "Nosocomial Bloodstream Infections i..."
...Candida species are the fourth leading cause of nosocomial bloodstream infection (BSI) in the United States, accounting for 8% to 10% of all BSIs acquired in the hospital (321)....
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...Candida infections are associated with a high crude mortality of 46% to 75%, reflecting the severe underlying illnesses of the infected patients (59, 67, 70, 195, 321)....
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TL;DR: The importance of fungi as human pathogens is highlighted and the challenges the authors face in combating the devastating invasive infections caused by these microorganisms are discussed, in particular in immunocompromised individuals.
Abstract: Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.
3,125 citations
Cites background from "Nosocomial Bloodstream Infections i..."
...Indeed, Candida species are the fourth most common cause of nosocomial (hospital-acquired) bloodstream infections (13), and advanced medical procedures—such as the use of catheters, neonatal intensive care, major gut surgery, or liver transplantation—are predisposing factors to disseminated Candida infections....
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TL;DR: This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of S. aureus as a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections.
Abstract: Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.
3,054 citations
References
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3,079 citations
TL;DR: The data suggest that clinical efforts should be aimed at reducing the administration of inadequate antimicrobial treatment to hospitalized patients with bloodstream infections, especially individuals infected with antibiotic-resistant bacteria and Candida species.
1,757 citations
"Nosocomial Bloodstream Infections i..." refers background in this paper
...[30] showed that mortality rates doubled, from 30% to 60%, when inappropriate empirical antibiotic therapy was given to ICU patients with BSIs....
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TL;DR: Given the increasing multidrug resistance among staphylococci and the possible emergence of vancomycin-resistant strains, global strategies are needed to control emergence and spread of multiply resistant staphlyococci.
Abstract: Between January 1997 and December 1999, bloodstream isolates from 15,439 patients infected with Staphylococcus aureus and 6350 patients infected with coagulase-negative Staphylococcus species (CoNS) were referred by SENTRY-participating hospitals in the United States, Canada, Latin America, Europe, and the Western Pacific region. S. aureus was found to be the most prevalent cause of bloodstream infection, skin and soft-tissue infection, and pneumonia in almost all geographic areas. A notable increase in methicillin (oxacillin) resistance among community-onset and hospital-acquired S. aureus strains was observed in the US centers. The prevalence of methicillin (oxacillin)-resistant S. aureus varied greatly by region, site of infection, and whether the infection was nosocomial or community onset. Rates of methicillin resistance were extremely high among S. aureus isolates from centers in Hong Kong and Japan. Uniformly high levels of methicillin resistance were observed among CoNS isolates. Given the increasing multidrug resistance among staphylococci and the possible emergence of vancomycin-resistant strains, global strategies are needed to control emergence and spread of multiply resistant staphylococci.
1,397 citations
TL;DR: Concurrent surveillance for nosocomial bloodstream infections at 49 hospitals over a 3-year period detected >10,000 infections, and coagulase-negative staphylococci were the most common pathogens on all clinical services except obstetrics, where Escherichia coli was most common.
Abstract: Nosocomial bloodstream infections are important causes of morbidity and mortality. In this study, concurrent surveillance for nosocomial bloodstream infections at 49 hospitals over a 3-year period detected >10,000 infections. Gram-positive organisms accounted for 64% of cases, gram-negative organisms accounted for 27%, and 8% were caused by fungi. The most common organisms were coagulase-negative staphylococci (32%), Staphylococcus aureus (16%), and enterococci (11%). Enterobacter, Serratia, coagulase-negative staphylococci, and Candida were more likely to cause infections in patients in critical care units. In patients with neutropenia, viridans streptococci were significantly more common. Coagulase-negative staphylococci were the most common pathogens on all clinical services except obstetrics, where Escherichia coli was most common. Methicillin resistance was detected in 29% of S. aureus isolates and 80% of coagulase-negative staphylococci. Vancomycin resistance in enterococci was species-dependent-3% of Enterococcus faecalis strains and 50% of Enterococcus faecium isolates displayed resistance. These data may allow clinicians to better target empirical therapy for hospital-acquired cases of bacteremia.
1,396 citations
"Nosocomial Bloodstream Infections i..." refers background or methods in this paper
...In addition, antibiotic resistance rates have been rising during the past 2 decades for all predominant organisms, including Staphylococcus aureus [14, 16, 17], coagulase-negative staphylococci [18, 19], enterococci [20], and gram-negative pathogens [15, 21, 22]....
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...gram-positive organisms have become increasingly frequent [2, 14, 15]....
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...The Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE) Project is based at Virginia Commonwealth University in Richmond, Virginia, and includes 49 hospitals of various sizes (range, 60–1200 beds) that are geographically dispersed throughout the United States (figure 1) [14, 24]....
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TL;DR: The attributable mortality from nosocomial bloodstream infection is high in critically ill patients and is associated with a doubling of the SICU stay, an excess length of hospital stay of 24 days in survivors, and a significant economic burden.
Abstract: Objective. —To determine the excess length of stay, extra costs, and mortality attributable to nosocomial bloodstream infection in critically ill patients. Design. —Pairwise-matched (1:1) case-control study. Setting. —Surgical intensive care unit (SICU) in a tertiary health care institution. Patients. —All patients admitted in the SICU between July 1,1988, and June 30, 1990, were eligible. Cases were defined as patients with nosocomial bloodstream infection; controls were selected according to matching variables in a stepwise fashion. Methods. —Matching variables were primary diagnosis for admission, age, sex, length of stay before the day of infection in cases, and total number of discharge diagnoses. Matching was successful for 89% of the cohort; 86 matched case-control pairs were studied. Main Outcome Measures. —Crude and attributable mortality, excess length of hospital and SICU stay, and overall costs. Results. —Nosocomial bloodstream infection complicated 2.67 per 100 admissions to the SICU during the study period. The crude mortality rates from cases and controls were 50% and 15%, respectively (P Conclusions. —The attributable mortality from nosocomial bloodstream infection is high in critically ill patients. The infection is associated with a doubling of the SICU stay, an excess length of hospital stay of 24 days in survivors, and a significant economic burden. (JAMA. 1994;271:1598-1601)
1,381 citations