Although terms such as infection, infectious disease, subclinical infection, and colonization are used frequently, the subtleties of these terms often are confusing. The term “infection” implies the successful multiplication of a microbe on or within a host. The term “infectious disease” applies when signs and symptoms result from infection and its associated damage or altered physiology (1,18).

If the infection provokes an immune response only, without overt clinical disease, it is a “subclinical or inapparent infection.” “Colonization” implies the presence of a microorganism in or on a host with growth and multiplication of the microorganism but without any overt clinical expression or detected immune reaction at the time it is isolated (1). “Subclinical or inapparent infection” refers to a relation between the host and microorganism in which the microorganism is present; there is no overt expression of the presence of the microorganism, but there is interaction between the host and microorganism that results in a detectable immune response, such as a serologic reaction, a skin test conversion, or a proliferative response of white blood cells to antigens from infecting organisms (1). Therefore, special tests to detect immune responses may be needed to differentiate colonization from subclinical infection. In many instances, there is an absence of such data and the situation is considered colonization.

A carrier (or colonized person) is an individual colonized with a specific microorganism and from whom the organism can be recovered (i.e., cultured) but who shows no overt expression of the presence of the microorganism at the time it is isolated (1,19); a carrier may have a history of previous disease due to that organism, such as typhoid.

Colonization is a natural process in the development of natural flora. In the neonate, this process occurs within days to weeks of delivery after which the neonate’s normal flora is similar to that seen in adults (19). Whether colonization occurs long or immediately before infection, it can play a major role in the development of HAIs. In many instances, colonization is a necessary precedent to infection. It is worth discussing colonization in more detail since there is heated discussion in the infection control/healthcare epidemiology community about screening for colonization with MDROs and the role and extent of isolation policies/practices. Those who advocate screening and aggressive infection control practices/isolation contend that colonized patients represent a large predominately unrecognized population who can serve as an unchecked reservoir for infection and that once the proportion of colonization patients reaches a threshold, this may lead to high burden of infection with these MDROs for which antimicrobial treatments are limited (20,21). Those who oppose these screening programs point to limited resources/cost, competing emerging issues and the concerns about the strength of studies/data to support these efforts and practices (22). A recent study found when patients with methicillin-resistant Staphylococcus aureus (MRSA) and other antibiotic-resistant bacteria are isolated in the hospital, these contact precautions may reduce the number of visits by HCWs and outside visitors, but also increased compliance with hand hygiene upon exit of patients’ rooms. Fewer visits and increased hand hygiene are important in preventing the spread HAIs, but clinicians and epidemiologists need to consider both the positive and negative aspects of these interventions, including the effect to patients’ mental well-being and perception of care, whether patients are isolated for any MDRO or other pathogen (23).

Dissemination, or shedding of microorganisms, refers to the movement of organisms from a person carrying them into the immediate environment (1). This could be illustrated by culture samples of air, or surfaces, or other inanimate objects onto which microorganisms from the carrier may have been deposited. Shedding studies may be conducted in specially constructed chambers designed to quantitate dissemination. While shedding studies occasionally have been useful to document unusual dissemination (24), they have generally not been useful in identifying carriers whose dissemination has resulted in infection in other persons. In the hospital setting, dissemination is most effectively identified by means of HAI surveillance in which the occurrence of infection among contacts is noted.

In some hospitals, culture surveys of all or selected asymptomatic staff may be conducted in an attempt to identify carriers of certain organisms. Even in outbreak settings, such surveys lack practical relevance, can be costly, and can actually be misleading. This practice identifies only those who are culture-positive and does not in itself reliably separate colonized persons into disseminators vs. nondisseminators. The practice could erroneously identify a HCW as the “source” and
have serious ramifications for his or her future. Instead, culture surveys should be directed by sound surveillance and epidemiologic investigation to identify the potential source (25). Additional laboratory studies to confirm the presence of a suspected HCW or patient disseminator may then be undertaken.

In some instances, dissemination from a carrier has been reported to be influenced by the occurrence of an unrelated disease such as a second infection (26). One report, for example, suggested that infants carrying staphylococci in their nares disseminate staphylococci only after the onset of a viral respiratory infection. Such infants are called cloud babies. In another instance, a physician disseminated staphylococci from his skin because of a reactivation of chronic dermatitis. Desquamation of his skin led to the transmission of staphylococci (probably by skin squames) to patients with whom he had contact. Dissemination of tetracycline-resistant S. aureus from individuals carrying this organism who were treated with tetracycline has been reported. The risk of dissemination is generally greater from individuals with disease caused by that organism than from individuals with subclinical infection or colonization with the organism (26).

“Contamination” refers to microorganisms that are transiently present on body surface (e.g., hands) without tissue invasion or physiologic reaction. Contamination also refers to the presence of microorganisms on or in an inanimate object.

In early editions of this text, the terms hospital-acquired or nosocomial infections would have been used, with the definition for hospital-acquired/nosocomial infections as infections that develop within a hospital or are produced by microorganisms acquired during hospitalization. As discussed previously, the delivery and scope of healthcare and healthcare epidemiology is expanding. The CDC defines HAIs as infections that patients acquire during the course of receiving treatment for other conditions or that HCWs acquire while performing their duties within a healthcare setting (4). In this spirit, even the branch of CDC that was formally the Hospital Infections Program broadened its name to the Division of Healthcare Quality Promotion to reflect this sentiment in the last decade (4).

The CDC’s National Nosocomial Infections Surveillance (NNIS) system was developed in the early 1970s to monitor the incidence of HAIs and their associated risk factors and pathogens (27,28). The NHSN was established in 2005 to integrate NNIS with two other CDC surveillance systems, the Dialysis Surveillance Network, and the National Surveillance System for Healthcare Workers. NHSN data collection, reporting, and analysis are organized into three components: Patient Safety, Healthcare Personnel Safety, and Biovigilance, and use standardized methods and definitions in accordance with specific module protocols. Decades ago NNIS had only about 300 facilities, NHSN now has >11,000 participating facilities (29,30).

Although the NHSN system is for HAI surveillance purposes and NHSN definitions are not necessarily to be held as a gold standard for clinical/therapeutic decisions, some important points about HAIs can be illustrated by NHSN (and former NNIS) experience and definitions (28,29). The first is that a major factor that specifically separates epidemiology and HAIs from other infectious diseases is that there is a quest to step away from a single patient and to standardize definitions to consistently identify trends in HAIs. In beginning to identify a cluster or outbreak, one of the early and consistent steps is to try to find a definition as to what constitutes a “case” of the HAI in question. Use of uniform definitions is critical if data collected are to be used for intra- or interfacility comparisons or to data from aggregated systems (e.g., NHSN) (27,28,29).

The NHSN system defines an HAI as a localized or systemic condition that results from adverse reaction to the presence of an infectious agent(s) or its toxin(s), which was not present or incubating at the time of admission to the hospital/facility. For bacterial HAIs, this means that the infection usually becomes evident ≥48 hours (i.e., the typical incubation period) after admission. Since incubation periods vary with type of pathogen and patient’s underlying disease, each infection must be assessed individually.

Two special situations that are usually HAIs are infection in a neonate that results from passage through the birth canal and infection that is acquired in the hospital but does not become evident until after hospital discharge. The majority of HAIs becomes clinically apparent while the patients are still in the facility; however, different studies have given widely varying estimates that between 12% and 84% of surgical site infections (SSIs) are detected after discharge from the hospital (31). Since the length of postoperative stay continues to decrease, many SSIs may not be detected for several weeks after discharge and may not require readmission to the hospital where the operation occurred. In these instances, the patient became colonized/infected while in the hospital, but the incubation period was longer than the patient’s hospital stay. This sequence also is seen in some infections of newborns and in most breast abscesses of new mothers (since the length of postpartum stay also is brief).

Two special situations that usually are not considered HAIs are the complication or extension of infection(s) already present on admission unless a change in pathogen or symptoms strongly suggests the acquisition of new infection and the infection in an infant that is known or proven to have been acquired transplacentally (e.g., toxoplasmosis, syphilis) and becomes evident ≤48 hours after birth. Infections incubating at the time of the patient’s admission to the facility are not considered HAIs; they are community-acquired, unless they result from a previous healthcare exposure. However, community-acquired infections can serve as a ready source of infection for other patients or HCWs and thus must be considered in the total scope of hospital-related infections.

Two important principles of HAIs relate to infections that are preventable vs. those that are nonpreventable. The term preventable HAI implies that some event related to the infection could have been altered and that such alteration would have prevented the infection from occurring. A HCW who does not perform hygiene on his or her hands between contacts with the urinary collection equipment of two patients, for example, may transmit pathogens from the first patient to the second, which may result in a urinary tract infection (UTI). Hand hygiene might have prevented this infection from occurring. The identification of such an event in retrospect, however, is difficult; it is necessary to distinguish this situation from circumstances in which both patients developed infections from their own endogenous flora (e.g., from Escherichia coli). It often is impossible to identify the precise mode of acquisition of individual HAIs. More than one mode of transmission may
contribute to the development of the same infection, and not all modes may be preventable.

A nonpreventable infection is one that will occur despite all possible precautions, for example, infection in an immunosuppressed patient due to endogenous flora. In the past it had been estimated that approximately 30% of all reported HAIs are preventable (1); however, more recent studies documenting the near elimination of CLA-BSIs in ICU patients suggest that an even higher percentage of HAIs may be preventable (8,13). Many facilities and regions are teaming up and initiating infection prevention bundles that focus on some combination of hand hygiene, maximal barrier precautions, chlorhexidine with alcohol skin antisepsis, optimal site selection, and proper maintenance/daily review/device removal whenever possible. Outbreaks, especially those caused by a common vehicle, potentially are preventable; however, outbreaks/clusters account for only a small number of HAIs (5% to 10% of all HAIs) (32,33). Prompt investigation and the institution of rational control measures should reduce the extent of the epidemic. Endemic infections account for the majority of HAIs, and the consistent application of recognized, effective control and prevention measures for endemic infections probably is the single most important factor in reducing the overall level of HAIs.

Two terms, endogenous (autogenous) and exogenous, are helpful in understanding HAIs. Endogenous infections are caused by the patient’s own flora; exogenous infections result from transmission of organisms from a source other than the patient. For endogenous infections, the patient either was admitted to the facility colonized with these microorganisms or became colonized at some point during his or her stay at the hospital/facility after admission. It may not always be possible to determine whether a particular organism isolated from a patient with an HAI caused by that organism is exogenous or endogenous, and the term autogenous should be used in this situation. Autogenous infection indicates that the infection was derived from the flora of the patient, whether or not the infecting organism became part of the patient’s flora subsequent to admission (1). Information about current infectious diseases/microorganism problems in the community or in hospital contacts may be useful in differentiating the two sources. For example, in the past, if a patient had an infection with MRSA, it probably would have been assumed that this infection was related to acquisition in the healthcare facility. In the last several years, however, episodes of community-acquired MRSA (34,35) have increased and it may be helpful to know the local occurrence of these community-acquired isolates in addition to the patient’s recent healthcare-related and antimicrobial exposures. Microbiologic characteristics of the organism such as antibiograms, biochemical testing, susceptibility patterns, and molecular typing (e.g., pulsed-field gel electrophoresis) may provide additional evidence to support healthcare-associated vs. community origin of these strains/infections.

Often possible clusters of HAIs are detected through clinical microbiology, or infection control surveillance data, or by an astute laboratorian or clinician (25,36). Once a cluster is detected, one must evaluate whether this represents a problem, such as an outbreak. As discussed previously, exploring cases and arriving at a case definition is essential to identify as many cases as possible. Comparing the rate of the event during the cluster to a period before the cluster can establish whether an outbreak is occurring. A few definitions are helpful to characterize disease frequency, including sporadic, endemic (hyperendemic), outbreak, and epidemic.

“Sporadic” means that episodes occur occasionally and irregularly without any specific pattern. “Endemic” means that the disease occurs with ongoing frequency in a specific geographic area in a finite population and over a defined time period. “Hyperendemic” refers to what appears to be a gradual increase in the occurrence of a disease in a defined area beyond the expected number; however, it may not be certain whether the disease will occur at epidemic proportions. An “epidemic” is a definite increase in the incidence of a disease above its expected endemic or background rate. “Outbreak” often is used interchangeably with epidemic; however, many use outbreak to mean an increased rate of occurrence but not at levels as serious as an epidemic (1).

An occasional gas gangrene infection among postoperative patients is an example of a sporadic infection. An endemic HAI is represented by the regular occurrence of infections either in a particular site or at different sites that are due to the same organism, occur at a nearly constant rate, and are generally considered by the hospital staff to be within expected and acceptable limits. SSIs due to a single organism that follow operations classified as “contaminated surgery,” for example, could represent the endemic level of SSIs. The recent high levels of C. difficile infections with the B1NP1 strain in facilities have been referred to as the hyperendemic strain (37). In hospitals or healthcare facilities, most outbreaks are small clusters. Outbreaks will be discussed in detail later in this chapter and text.

Plotting a histogram of the distribution of “cases” by time in an “epidemic curve” may aid in confirming the existence of an outbreak (vs. sporadic or endemic infections) and developing hypotheses about the mode of transmission (25,38,39). This can be simply executed on graph paper or by using a variety of software packages, such as Microsoft Excel or PowerPoint. Details on the construction of an epidemic curve are described in the descriptive epidemiology section (also Table 1.2 and Figure 1.1).

To identify that a problem with HAIs exists, it is important to be able to quantify the frequency of disease/event occurrence (counting cases). The two most commonly used measures of disease frequency are prevalence and incidence. Some unique issues that may occur with HAIs related to these measures of frequency will be reviewed, and some additional measures of incidence (incidence density and cumulative incidence) and prevalence are discussed. Each of these measures has uses in healthcare epidemiology and advantages and disadvantages (Table 1.1).

Incidence is the number of new cases in a specific population in a defined time period (see Chapter 6) (40). Prevalence is a measure of status rather than newly occurring disease and of people who have the disease at a specific time (see Chapter 7) (40).

Incidence can be described in several ways. Incidence density (also known as the incidence rate) is the number of new events (disease onset) in a specified amount of person-time (hospital or healthcare facility-days) in a population at risk (40,41). Incidence density usually is restricted to the first event (first HAI, i.e., BSI), since second events are not statistically independent events in the same individual (i.e., once the patient has had one HAI, he or she is more likely to have a second one). The population at risk includes all patients who have not yet had the first event. Once a patient acquires the first HAI, he or she would not still be a part of the population at risk and would be withdrawn. Patients who never have an HAI would contribute all their hospital-/facility-days to the pool of days at risk for a first event, but patients who became infected would contribute only those hospital-days before the onset of the first infection.

Since the first event is just a number, incidence density has the units of (1/time). In practical use in healthcare epidemiology, HAI rates usually are expressed as number of first events in 1,000 hospital-/facility-days (usually gives a single or double-digit number of events per 1,000 hospital-days) (41,42). The advantage of using incidence density is that it allows a way to correct for time and separate out the duration of exposure from the effect of daily risk. Examples where this is particularly useful in healthcare epidemiology are in comparisons of those with short vs. long hospital stays and for peripheral intravenous lines vs. central venous catheters (41,42). In each of these instances, the time at risk is substantially longer for the second group vs. the first.

A question that arises with the incidence density is what to do with a second or additional event (e.g., second HAI; i.e., second healthcare-associated BSI) since multiple studies has shown that the subsequent events are not independent. The first guidance is that for quantitative analysis of HAIs, it would be overly simplistic and misleading to sum these nonindependent events and put them over the denominator (41). The first and each subsequent event actually would be a risk factor for the next infection, which is why it is best to restrict analysis to the first event.

There are more complex methods to include first and multiple/subsequent events in a study using different stratum (43). For example, one approach is to define the population at risk differently for each occurrence (40): The population at risk for the first event would consist of individuals who have not experienced the disease before; the population
at risk for the second event or first recurrence would be limited to those who have experienced the event (infection) once and once only, and so on. An individual should contribute time to the denominator of the incidence rate for first events only until the time that the disease first occurs. At that point, the individual should cease contributing time to the denominator of that rate and should begin contributing time to the denominator of the rate measuring the second occurrence. If and when there is a second event, the individual should stop contributing time to the rate measuring the second occurrence and begin contributing to the denominator of the rate measuring the third occurrence, and so forth.

Cumulative incidence is the proportion of all those at risk who ultimately suffer a first event (40,41,42). In traditional infectious disease epidemiology, this has been termed the attack rate (41). This is actually not a rate but a proportion. Cumulative incidence is derived from the incidence density and in simple terms could be thought of as the sum of all incidence densities for first events over all of the person-time at risk for the first event. This is a simple proportion and thus has no units. For overall HAIs, the time implied is the course of hospitalization (duration in the facility) until the first event or discharge without first event. There are a few limitations to the cumulative incidence. First, there should be follow-up for all at risk to determine whether they have the first event. However, patients do not all have the same length of hospital stay or remain at risk for the same amount of time. Also, HAIs are time related, and comparing HAI rates among patients with differing lengths of stay can be misleading. The cumulative incidence could be of particular use with an HAI considered to be from a point-source, such as a contaminated fluid or SSI (operation as the point-source) (41,42).

In the past, HAIs were reported as a cumulative incidence of number of infections per 100 discharges. One disadvantage of this aggregation and presentation is that there was no distinction between separate first infection from multiple infections in the same patients (thus, 10 infections per 100 discharges could be 10 infections from one very complicated patient, 10 from 10 different healthy patients, or some description between these extremes; the extremes illustrate how this summary term could be quite different in its clinical and epidemiological relevance and in what intervention methods might be necessary). Another disadvantage is that since one patient could be counted multiple times, this would not take into account lack of statistical independence, thus making comparisons difficult (41).

Unlike incidence measures, which focus on events, prevalence focuses on disease status. “Prevalence” is defined as the proportion of a population that has disease at a specific point in time (42). Several terms, such as point prevalence, prevalence proportion, and prevalence rate, often are used interchangeably. Prevalence depends on the incidence and the duration of the disease. As either of these increases, the prevalence increases. The main useful measure for healthcare epidemiology would be point prevalence for studies such as a cross-sectional study (30) (i.e., a point-prevalence survey on a day using cultures to detect colonization/infections with an MDRO, such as vancomycin-resistant Enterococcus [VRE], Carbapenem-resistant Enterobacteriaceae [CRE], or MRSA). This could give an idea of the burden of a problem at a particular point in time to assist in defining that a problem exists, guide decisions to pursue additional studies, and allow for allocation of resources. Of note, populations are dynamic and since individuals are entering and leaving the population, the prevalence can vary based on when it is measured.