Nosocomial Infection – a Historical Perspective (1998)

As we enter the next millennium of infection control, we stand on the
shoulders of giants—Jenner, Semmelweis, Nightingale, Oliver Wendell Holmes,
and my own personal favorite, Thomas Crapper, the father of indoor
plumbing. Modern infection control is grounded in the work of Ignaz
Semmelweis, who in the 1840s demonstrated the importance of hand hygiene
for controlling transmission of infection in hospitals. However, infection
control efforts were spotty for almost a century.


In 1976, the Joint Commission on Accreditation of Healthcare Organizations published
accreditation standards for infection control, creating the impetus and
need for hospitals to provide administrative and financial support for
infection control programs. In 1985, the Centers for Disease Control and
Prevention’s (CDC’s) Study on the Efficacy of Nosocomial Infection Control
reported that hospitals with four key infection control components—an
effective hospital epidemiologist, one infection control practitioner for
every 250 beds, active surveillance mechanisms, and ongoing control
efforts—reduced nosocomial infection rates by approximately one third (1).

Over the past 25 years, CDC’s National Nosocomial Infections Surveillance
(NNIS) system has received monthly reports of nosocomial infections from a
nonrandom sample of United States hospitals; more than 270 institutions
report. The nosocomial infection rate has remained remarkably stable
(approximately five to six hospital-acquired infections per 100
admissions); however, because of progressively shorter inpatient stays over
the last 20 years, the rate of nosocomial infections per 1,000 patient days
has actually increased 36%, from 7.2 in 1975 to 9.8 in 1995 (Table 1). It
is estimated that in 1995, nosocomial infections cost $4.5 billion and
contributed to more than 88,000 deaths—one death every 6 minutes.

Which Nosocomial Infections Are Emerging?

We have witnessed a cyclical parade of pathogens in hospitals. In Semmelweis’s
era, group A streptococci created most nosocomial problems. For the next 50 to
60 years, gram-positive cocci, particularly streptococci and Staphylococcus
aureus, were the hospital pathogens of major concern. These problems
culminated in the pandemic of 1940 to 1950, when S. aureus phage type 94/96
caused major nosocomial problems. In the 1970s, gram-negative bacilli,
particularly Pseudomonas aeruginosa and Enterobacteriaceae, became
synonymous with nosocomial infection. By the late 1980s and early 1990s,
several different classes of antimicrobial drugs effective against gram-negative
bacilli provided a brief respite. During this time, methicillin-resistant S. aureus
(MRSA) and vancomycin-resistant enterococci (VRE) emerged, signaling the
return of the “blue bugs.” In 1990 to 1996, the three most common
gram-positive pathogens—S. aureus, coagulase-negative staphylococci, and
enterococci—accounted for 34% of nosocomial infections, and the four most
common gram-negative pathogens—Escherichia coli, P. aeruginosa, Enterobacter
spp., and Klebsiella pneumoniae—accounted for 32% (3).

Bloodstream infections and pneumonias have increased in frequency from 1975
to 1996 (Table 2). However, tracking nosocomial infections by site has
become difficult in the last few years because of shorter inpatient stays.
For example, the average postoperative stay, now approximately 5 days, is
usually shorter than the 5- to 7-day incubation period for S. aureus
surgical wound infections.

Acquired antimicrobial resistance is the major anticipated problem in hospitals.
VRE and MRSA are the major gram-positive pathogens of concern (5,6). P.
aeruginosa, Klebsiella, and Enterobacter that harbor chromosomal or
plasmid-mediated beta-lactamase enzymes are the major resistant
gram-negative pathogens. The contribution of antibiotic resistance to excessive
death rates in hospitals is difficult to evaluate, often depending on whether
studies are population-based or case-control, but evidence is mounting that
antimicrobial resistance contributes to nosocomial deaths.

While bacterial resistance is clearly the major threat, viral and fungal
resistance could become important because of the small number of
therapeutic options for these pathogens. Herpes viruses with acquired
resistance to acyclovir and ganciclovir have emerged as problems,
particularly in HIV-infected patients. Pathogens with intrinsic resistance
often have lower pathogenicity and have disproportionately affected
immunocompromised patients. For example, Candida spp. with intrinsic
resistance to azole antifungal agents (e.g., C. krusei) and to amphotericin
B (e.g., C. lusitaniae) have emerged as problem pathogens in oncology

While we are facing the era of opportunists, including fungi, viruses, and
parasites in immunocompromised patients, the one we fear most is the
postantibiotic era. The first nosocomial inkling is MRSA with reduced
susceptibility to vancomycin (7). Beyond the postantibiotic era lies the
era of xenogenic infections as organs, transplanted from nonhuman primates,
bring with them a variety of potential zoonotic pathogens. Nevertheless,
traditional respiratory pathogens may yet prove to be our greatest
challenge; for example, a major shift in strain type (8) could result in
devastating pandemic community and nosocomial influenza A outbreaks.

Who Is Affected by Emerging Nosocomial Pathogens?

Nosocomial infections typically affect patients who are immunocompromised
because of age, underlying diseases, or medical or surgical treatments.
Aging of our population and increasingly aggressive medical and therapeutic
interventions, including implanted foreign bodies, organ transplantations,
and xenotransplantations, have created a cohort of particularly vulnerable
persons. As a result, the highest infection rates are in intensive care
unit (ICU) patients. Nosocomial infection rates in adult and pediatric ICUs
are approximately three times higher than elsewhere in hospitals. The sites
of infection and the pathogens involved are directly related to treatment
in ICUs. In these areas, patients with invasive vascular catheters and
monitoring devices have more bloodstream infections due to
coagulase-negative staphylococci. In fact, most cases of occult bacteremia
in ICU patients are probably due to vascular access-related infections.
Fungal urinary tract infections have also increased in ICU patients,
presumably because of extensive exposure to broad-spectrum antibiotics. In
the National Nosocomial Infections Surveillance system, Candida spp. are
the main cause of nosocomial urinary infections in ICUs (9).

Why Are Nosocomial Infections Emerging Now?

Three major forces are involved in nosocomial infections. The first is
antimicrobial use in hospitals and long-term care facilities. The increased
concern about gram-negative bacilli infections in the 1970s to 1980s led to
increased use of cephalosporin antibiotics. As gram-negative bacilli became
resistant to earlier generations of cephalosporin antibiotics, newer
generations were developed. Widespread use of cephalosporin antibiotics is
often cited as a cause of the emergence of enterococci as nosocomial
pathogens. About the same time, MRSA, perhaps also in response to extensive
use of cephalosporin antibiotics, became a major nosocomial threat.
Widespread empiric use of vancomycin, as a response to concerns about MRSA
and for treatment of vascular catheter-associated infection by resistant
coagulase-negative staphylococci, is the major initial selective pressure
for VRE. Use of antimicrobial drugs in long-term care facilities and
transfer of patients between these facilities and hospitals have created a
large reservoir of resistant strains in nursing homes.

Second, many hospital personnel fail to follow basic infection control,
such as hand washing between patient contacts. In ICUs, asepsis is often
overlooked in the rush of crisis care (10).

Third, patients in hospitals are increasingly immunocompromised. The shift
of surgical care to outpatient centers leaves the sickest patients in
hospitals, which are becoming more like large ICUs (11). This shift has led
to the greater prevalence of vascular access associated bloodstream
infections and ventilator-associated pneumonias.

Other precipitating factors also can be anticipated in hospitals.
Transplantation is a double-edged sword because of the combined effects of
immunosuppression of transplant patients and of infectious diseases that
come with some transplanted organs. The blood supply will continue to be a
source of emerging infectious diseases. Moreover, as hospitals age,
infrastructure repairs and renovations will create risks of airborne fungal
diseases caused by dust and spores released during demolition and
construction. Infections due to other pathogens, such as Legionella, may
also result from such disruptions.

How Can We Prevent and Control Emerging Nosocomial Infections?

Infection control can be very cost-effective. Approximately one third of
nosocomial infections are preventable. To meet and exceed this level of
prevention, we need to pursue several strategies simultaneously (12).
First, we need to continue to improve national surveillance of nosocomial
infections so that we have more representative data. We must assess the
sensitivity and specificity of our surveillance and of our case
definitions, particularly for difficult-to-diagnose infections like
ventilator-associated pneumonia. We also need to develop systems for
surveillance of “nosocomial” infections that occur out of the hospital,
where much health care is now given.

Second, we need to ensure that surveillance uses are valid. The Joint
Commission on Accreditation of Healthcare Organization’s ORYX initiative
for monitoring health-care processes and outcomes will lead to core
indicators and sentinel event monitoring. This initiative will be followed
by increased outpatient surveillance, which ultimately may lead to
systemwide real-time surveillance and reporting. Because we want to use
nosocomial infection rates as a core indicator of quality of care, we need
to improve our ability to “risk adjust” infection rates so we know that our
interprovider and interhospital comparisons are valid. Risk stratification
will ultimately depend on organic-based computer systems that will mimic
biologic events.

Third, many of our successes in controlling nosocomial infections have come
from improving the design of invasive devices. This is particularly
important given the marked increase in frequency of vascular
access associated bloodstream infections, particularly in ICU patients.
Given the choice of changing human behavior (e.g., improving aseptic
technique) or designing a better device, the device will always be more
successful. Of particular importance is the development of noninvasive
monitoring devices and minimally invasive surgical techniques that avoid
the high risk associated with bypassing normal host defense barriers (e.g.,
the skin and mucous membranes).

Fourth, forestalling the postantibiotic era will require aggressive
antibiotic control programs (13); these may become mandated for hospitals
that receive federal reimbursements, as happened in the past with infection
control programs. Risks for antibiotic-resistant strains also may be
reduced in the future by controlling colonization through use of
immunization or competing flora.

Fifth, antimicrobial resistance problems and the advent of
xenotransplantation emphasize the importance of newer microbiologic
methods. For investigation of outbreaks of multidrug-resistant pathogens,
pulsed-field gel electrophoresis has become a routine epidemiologic tool
(14). Molecular epidemiologic analysis also may help us better understand
the factors that lead to the emergence of resistant strains. For diagnosis
of syndromes caused by unusual pathogens, representational difference
analysis and speciation by use of the pathogen’s phylogenetic r-RNA “clock”
may become routine.

Sixth, control of tuberculosis (TB) in hospitals is an excellent example of
the successful collaboration of the infection control community, CDC, and
regulatory agencies. But we can anticipate that the Occupational Safety and
Health Administration may have many new employee health issues beyond TB
and bloodborne pathogens to evaluate in hospitals, such as health problems
related to exposure to magnetic fields, to new polymers, and to medications
that contaminate the environment. Problems of mental stress due to
unrelenting exposure to pagers, faxes, e-mail, holograms, and telephonic
implanted communicators will require special attention.


Several enduring truths characterize the field of infection control.
Hospitals will become more like ICUs, and more routine care will be
delivered on an outpatient basis. Given the choice of improving technology
or improving human behavior, technology is the better choice. All infection
control measures will need to continue to pass the test of the “four Ps”
(15): Are the recommendations Plausible biologically (e.g., is it likely to
work)? Are they Practical (e.g., are they affordable)? Are they Politically
acceptable (e.g., will the administration agree)? And, will Personnel
follow them (e.g., can they and will they)?

The major advances in overall control of infectious diseases have resulted
from immunization and improved hygiene, particularly hand washing. We must
work with hospital personnel on better implementation of existing infection
control technologies so that we will not need to rely solely on technologic

Dr. Weinstein is chair, Division of Infectious Diseases, Cook County
Hospital; director of Infectious Diseases Services for the Cook County
Bureau of Health Services; and professor of Medicine, Rush Medical College.
He also oversees the CORE Center for the Prevention, Care and Research of
Infectious Disease and directs the Cook County Hospital component of the
Rush/Cook County Infectious Disease Fellowship Program. His areas of
research include nosocomial infections (particularly the epidemiology and
control of antimicrobial resistance and infections in intensive care units)
and health-care outcomes for patients with HIV/AIDS.


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Emerging Infectious Diseases
National Center for Infectious Diseases
Centers for Disease Control and Prevention
Atlanta, GA

[Emerging Infectious Diseases]
[Volume 4 No. 3 / July – September 1998]

Robert A. Weinstein
Cook County Hospital & Rush Medical College, Chicago, Illinois, USA

The Centers for Disease Control and Prevention (CDC) is one of the 13 major operating components of the Department of Health and Human Services (HHS), which is the principal agency in the United States government for protecting the health and safety of all Americans and for providing essential human services, especially for those people who are least able to help themselves.

Since it was founded in 1946 to help control malaria, CDC has remained at the forefront of public health efforts to prevent and control infectious and chronic diseases, injuries, workplace hazards, disabilities and environmental health threats.