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The question of why vancomycin-resistant enterococci (VRE) became epidemic in the United States can be answered on at least three basic levels: (1) molecular and genetic, (2) factors affecting host-microbe interactions, and (3) epidemiological. This article will address the epidemiological issues and seek to defend the assertion that, once VRE had evolved, its spread throughout hospitals in the United States was all but assured. Nosocomial VRE outbreaks were reported first in the mid- and late-1980s. Since that time, scientific reports of VRE have increased over 20-fold. Among hospitals participating in the National Nosocomial Infection Surveillance System from 1989 to 1997, the percentage of enterococci reported as resistant to vancomycin increased from 0.4% to 23.2% in intensive-care settings and from 0.3% to 15.4% in non-intensive-care settings. Factors leading to the spread of VRE in US hospitals include (1) antimicrobial pressure, (2) sub-optimal clinical laboratory recognition and reporting, (3) unrecognized “silent” carriage and prolonged fecal carriage, (4) environmental contamination and survival, (5) intrahospital and interhospital transfer of colonized patients, (6) introduction of unrecognized carriers from community settings such as nursing homes, and (7) inadequate compliance with hand washing and barrier precautions. Guidelines developed by the Centers for Disease Control and Prevention's Hospital Infection Control Practices Advisory Committee address each of these factors. The impact of these guidelines on the spread of VRE within individual institutions has been variable, and the overall impact of the guidelines nationally is unknown.
There are major differences in the epidemiology of vancomycin-resistant enterococci (VRE) between the United States and Europe. In contrast with Europe, VRE in the United States are resistant to many antibiotics, and there appears to be less genetic variability among these isolates. European VRE of human origin are usually susceptible to many other antibiotics and are highly polyclonal. These clinical isolates have the same susceptibility profiles as VRE isolated from animals.
The differences in the spread of VRE between the United States and Europe might be explained by the overconsumption of glycopeptides and other antibiotics in hospitals in the United States and the use of avoparcin as a growth promotor in Europe.
The control of methicillin-resistant Staphylococcus aureus (MRSA) is still an unresolved issue in numerous healthcare institutions worldwide. Guidelines for the control of MRSA in hospitals focus on measures to control cross-transmission and prevent colonization, but rarely specifically mention the control of antimicrobial use. We reviewed the different types of evidence for a causal relationship between MRSA and antimicrobial use by classifying them in four categories: consistent associations, dose-effect relationships, concomitant variations, and arguments to support a plausible biological model to explain this relationship. Although the relative participation of cross-transmission and antimicrobial selection pressure in the level of MRSA observed in a healthcare setting remains to be determined, we found lines of evidence to support the existence of a relationship between MRSA and antimicrobial use in each of the four categories. This review points out the relative lack of studies specifically designed to investigate this aspect of MRSA epidemiology and the need to implement such studies quickly. In the meantime, the results presented here should encourage the implementation of antimicrobial-use improvement programs in hospitals in addition to existing infection control measures, which are still a priority in countries with high MRSA prevalence.
Improved diagnostic procedures should be an effective way to control infectious diseases and the spread of antibiotic resistance. To do so, diagnostics will need to be obtained within 1 hour of sampling and will require nucleic acid-based amplification tests directly on the clinical specimen.
A number of high-resolution molecular typing systems have been developed in recent years. Their availability raises the new issues of selecting the method(s) best suited for a particular purpose and interpreting and communicating typing results. Most of the currently available methods are comparative only: they allow testing of a sample of isolates for delineation of those closely related from those markedly different in genomic backgrounds. This approach is adequate for outbreak investigation, allowing determination of clonal spread in a microenvironment and identification of the source of infection. Comparative methods with sufficient resolution for most pathogens include restriction fragment-length polymorphism (RFLP), pulsed-field gel electrophoresis (PFGE), and arbitrarily primed and randomly amplified polymorphic DNA-polymerase chain reaction (PCR) analysis. For surveillance systems, monitoring clonal spread and prevalence in populations over extended periods of time requires library typing systems. These must be standardized, must have a high throughput, and must use a uniform nomenclature. Promising or validated methods include serotyping, insertion sequence fingerprinting, ribotyping, PFGE, amplified fragment-length polymorphism (AFLP), infrequent-restriction-site amplification PCR, interrepetitive element PCR typing (rep-PCR) and PCR-RFLP of polymorphic loci. PCR methods generating arrays of size-specific amplicons (AFLP, rep-PCR) can be more reproducibly analyzed by using denaturing polyacrylamide gel or capillary electrophoresis with automated laser detection. Binary probe typing systems appear optimal and should be enhanced further through use of DNA chip technology. In these systems, amplification of polymorphic regions is followed by solid-phase hybridization with a reference panel of sequence-variant specific probes. The resulting binary type results allow determination of reproducible, numeric profiles. However, interpretation and nomenclature of typing results for large-scale surveillance purposes still require a better understanding of population structure and microevolution of most microbial pathogens.
Mathematical models of disease transmission are being used increasingly in the design of population-based vaccination programs. Their use is illustrated in a review of some modeling studies that have implications for the use of measles, mumps, and rubella vaccine. Investigations of vaccination strategy options yield predictions for effectiveness and cost-effectiveness analyses. A quantitative understanding of the factors affecting disease transmission enables the setting of targets for vaccination programs and underpins disease elimination initiatives.
Immunocompromised patients are at high risk for opportunistic infections. Traditionally, these infections were thought to arise from endogenous reactivation of previously acquired latent infections, and nosocomial transmission therefore was deemed to be so unlikely that no special infection control interventions were needed to prevent transmission in healthcare settings. However, new data have challenged this view and suggest that some opportunistic pathogens are transmissible from one immunosuppressed patient to another. Epidemiological investigations, molecular genotyping, animal studies, and air-sampling experiments lend support to the hypothesis that reinfection with opportunistic pathogens does occur, that airborne transmission is possible, and that nosocomial spread is a plausible explanation for case clusters. Taken together, these observations support the view that some opportunistic infections are exogenous in origin and that additional epidemiological investigations are needed to define the true risk of nosocomial spread and need for isolation.
Streptococcus pneumoniae is most prominently a major cause of community-acquired infections of the respiratory tract, central nervous system, and bloodstream, but there is an increasing interest in its role in the epidemiology of hospital-acquired infections. Penicillin-resistant pneumococcal strains appeared 3 decades ago and now are present worldwide, often displaying multiple resistance due to antibiotic selective pressure. Horizontal spread can cause either sporadic cases or hospital outbreaks, primarily in younger children and elderly patients. Pneumococcal transmission from one patient to another can be documented by polymerase chain reaction or pulsed-field gel electrophoresis typing. Nosocomial acquisition of infection, along with pediatric age, previous hospitalization, and previous β-lactam therapy, are the main risk factors significantly associated with penicillin-resistant pneumococcal infections. Nosocomial acquisition also is associated with higher mortality from pneumo-coccal disease. The importance of penicillin resistance as a risk factor significantly associated with higher mortality from pneumococcal infection is found in some studies, but not in others. Mortality from pneumococcal pneumonia is approximately the same for human immunodeficiency virus (HIV)-infected patients without acquired immunodeficiency syndrome (AIDS) as for HIV-negative subjects, but it is significantly higher in AIDS patients. Penicillin-resistant strains are involved in the vast majority of hospital outbreaks, whether presenting as clinically manifest infection or a simple colonization. Pneumococcal vaccination is recommended universally in order to lower the incidence of invasive infection, although a number of problems can limit its effectiveness.
The role of coagulase-negative staphylococci (CNS) in bacteremias continues to be controversial. Until the 1970s, CNS were mostly recognized as contaminants, being part of the cutaneous flora. Since then, several studies have reported increasing incidence and severity of infections due to CNS.
To review the literature concerning the epidemiology of CNS bacteremia in the United States and Europe with reference to the multiple definitions of infection versus contamination, considering the effect of potential biases influencing the validity of the reported results.
Literature search of the MEDLINE database from January 1980 to February 1998. Studies with fewer than 500 episodes of bloodstream infections or fewer than 100 episodes of CNS bacteremia were not included in the pooled analysis.
(1) CNS remain the most frequent contaminants (58%-83% of positive blood cultures); (2) the proportion of all bloodstream infections caused by CNS is increasing (R=.51); (3) the overall incidence of true CNS bacteremia is increasing (R=.54, P=.0014); (4) comparing the United States to Europe, there is an increasing trend in the incidence of nosocomial bacteremia due to CNS in the United States (R=.82, P=.0006), but no trend is seen in European studies; (5) the mortality associated with true CNS bacteremia varies between 4.9% and 28%.
This review confirms the increasing importance of CNS bacteremias, measured both as a proportion and as an incidence of bloodstream infections. The contributions of several possible explanations for the incidence increase and the difference between the United States and Europe need further evaluation: (1) increased recognition and awareness of CNS infections among clinicians; (2) a gradual change in the definition of true bacteremia from an obligatory two positive blood cultures to one positive blood culture associated with a clinical picture compatible with infection; (3) a change in blood culture practices and techniques; (4) an increase in the numbers of blood cultures performed, which is reported both in the United States and in Europe; (5) a shift toward more elderly patients with increasingly severe underlying illnesses; and (6) increasing use of intravascular devices.
The apparent trend of increasing CNS bacteremia seems to be valid. Whether there is a real difference between the United States and Europe concerning the increase of CNS bacteremia is difficult to establish due to the large number of confounding factors. Few studies take into account the number of blood cultures performed or the use of intravascular devices to adjust for the observed trends. Further on-site surveillance studies are needed to investigate the phenomenon more extensively.