International Journal

Int. J. Hyg. Environ. Health 203, 153-157 (2000)

© Urban & Fischer Verlag
of Hygiene and
http://www.urbanfischer.de/journals/intjhyg Environmental Health

Epidemiologic methods for the prevention of nosocomial infections

Stephan Harbarth

Division of Infectious Diseases and Infection Control, Children’s Hospital, Harvard Medical School, Boston, USA

Received January 25, 2000 · Accepted July 18, 2000

Presented in part at the 4th Workshop on Nosocomial Infections of the Institute of Hygiene, Free University of Berlin, Berlin,
Germany, 15 January 2000.

Abstract
There is an ongoing controversy in Europe about the benefits and limitations of epidemiologic
methods for the prevention and control of hospital-acquired infections. Hospital epidemiology,
aimed at measuring the necessity, or effect, of preventive strategies for nosocomial infection con-
trol, is still an unknown field in many European institutions. The conceptual framework presented
here is not intended as a complete review of modern hospital epidemiology, but should be consid-
ered rather a viewpoint which tries to bridge the gap between microbiology-based hospital hygiene
and hospital epidemiology in Europe. The explanatory power and limitations of descriptive, ana-
lytical and interventional epidemiology are described. Based on the assumption that nosocomial in-
fections have causal and preventive factors that can be identified through systematic investigation,
epidemiologic methods add important knowledge to reduce hospital-acquired infections.

Key words: Epidemiology – nosocomial infections – prevention – hospital hygiene

Introduction
Is hospital epidemiology, as the study of the distribu-
tion, determinants and control of nosocomial infec-
tions (NI), just quantified common sense? Are hospital
epidemiologists only data-gathering adjuncts to the
medical community, without any focus on primary pre-
vention or basic hygiene concepts? In contrast, is old-
fashioned, environment-based hospital hygiene a weak
science, usually arising from the creation of a global
hypothesis, which is poetically elaborated upon by its
creator and his followers without any appeal to
patient-orientated facts that would be capable of con-
firming or refuting it?
Unfortunately, there has been a long-lasting contro-
versy in many European countries (especially in Ger-
many) about the benefits and limitations of epidemi-
ologic methods for the prevention and control of
hospital-acquired infections (Bitter-Suermann et al.,
1996). Hospital epidemiology, aimed at measuring the
necessity, or effect, of preventive strategies for NI con-
trol, is still an unknown topic in many institutions
throughout Europe (Gordts and Van Landuyt, 1998;
Ruef, 1999). The conceptual framework presented in
this article is intended neither as an expansion of the
ongoing debate, nor as a complete review of modern
hospital epidemiology, but should be considered rath-
er a viewpoint which tries to bridge the gap between
US-influenced hospital epidemiology and microbio-
logy-based hospital hygiene in Europe.

Corresponding author: Dr. Stephan Harbarth, Division of Infectious Diseases, Enders Bldg. 609, The Children’s Hospital, 300
Longwood Ave; Boston, MA 02115, USA, Phone: ++617 355 7621, Fax: ++617 355 8387, E-mail: harbarth@a1.tch.harvard.edu

1438-4639/00/203/2-153 $ 15.00/0
154 S. Harbarth
A strong motivation for this article is the often-heard
confusion about epidemiologic tools and their useful-
ness for the prevention of hospital-acquired infections,
since hospital hygienists and microbiologists appear to
have difficulty in appreciating the rules and discipline
of epidemiologic research (Kramer, 1999). Therefore,
based on a review of articles, this paper will emphasise
the importance of accurate epidemiologic methods for
studies of hospital-acquired infections. The explanato-
ry power of descriptive, analytical and experimental
epidemiology will be described. Finally, the shortcom-
ings and limitations of hospital epidemiology will be
discussed briefly.
The historic lesson
Experts in hospital hygiene and hospital epidemiolo-
gists plead and argue about the importance and
strengths of their respective fields, but still there is at
least one colleague whose scientific achievements and
insights into the cause and transmission of NI are im-
pressive. Amazingly, more than 150 years ago, Ignaz
Semmelweis (1818–1865) demonstrated the great im-
portance of epidemiologic observation and surveil-
lance in the prevention of NIs. In his epochal article
about the spread of puerperal fever (Semmelweis,
1861), Semmelweis cited four observations that led to
the introduction of hand hygiene using chlorinated
lime. Firstly, he noted that prior to 1823 (the year of
the introduction of anatomy classes into the Vienna
Medical School), the maternal mortality rate after de-
livery was much lower than afterwards. Secondly, he
observed that puerperal fever was more common on a
maternity ward where medical students worked than it
was on a ward where only midwives provided care.
Thus, he claimed that the students were contaminating
their hands while dissecting cadavers. Thirdly, he ob-
served the death of a colleague working in forensic
medicine, after accidentally being cut with a dissecting
knife and developing the same symptoms of sepsis as
did women dying of puerperal sepsis. Finally, he ob-
served 12 maternal deaths due to puerperal fever in a
ward where students had no contact with cadavers;
consequently, he deduced that cross-transmission by
living organisms must have occurred and insisted on
hand hygiene between every patient contact (Jarvis,
1994). Thus, Semmelweis made the crucial connection
between epidemiologic data and their impact on pa-
tient outcome, he performed accurate comparisons
with historic and contemporary control groups in
(nowadays called) cohort studies, and he ultimately
performed an interventional trial leading to the intro-
duction of hand disinfection. From that time on, inno-
vative physicians like J. Lister continued to practice
epidemiology in order to demonstrate a possible cause
and effect relation between NI and their prevention
(Gordts and Van Landuyt, 1998). Learning from these
seminal investigations based on the firm relation
between epidemiologic concepts and the prevention of
NI, a stop could be made to the disconcerting debate
about the benefits of hospital epidemiology. Never-
theless, we would like to elaborate on the following
question: For future research, how can epidemiologic
methods and the resulting evidence be used in order to
improve the control and prevention of hospital-acquir-
ed infections?
Descriptive epidemiology
NI occur rarely at random. Descriptive epidemiology
provides helpful tools to describe the general charac-
teristics of the distribution and frequency of NI, partic-
ularly in relation to persons, time and place. Informa-
tion on each of these characteristics can provide clues
leading to the formulation of a hypothesis about the
source, reservoir, or the mode and route of transmis-
sion of NI. This may help to evaluate the overall im-
portance, pattern and secular trends of NI occurring in
different settings, thus confirming or challenging pre-
vious knowledge.
In particular, descriptive data analysis may be per-
formed in the early phase of the investigation of clus-
ters of NI, using epidemiologic concepts such as case
definition, epidemic curve, and attack rate. By these
means, descriptive case series of NI help to identify un-
usual sources and modes of transmission. For instance,
the airborne transmission of Staphylococcus aureus
has been described in small clusters of staphylococcal
infections (Sherertz et al., 1996). Other examples of
unusual modes of transmission include series of pa-
tients infected by scrub nurses or surgeons with Candi-
da albicans or hepatitis C virus (Esteban et al., 1996;
Pertowski et al., 1995), highlighting the hazards of in-
fected health care personnel working in the operating
room.
Prevalence or cross-sectional surveys of NI are an-
other example of descriptive epidemiology. They give a
“snapshot” picture of NI clinically active during a giv-
en index day and provide information about the fre-
quency and characteristics of these infections. Such
data are easier, less expensive and less time-consuming
to perform than incidence studies and they provide im-
portant quantitative data for health policy research on
both a national and international level (Pittet et al.,
1999b; Ruef, 1997; Vincent et al., 1995). In addition,
the efficacy of infection control policies can be easily
measured by repeated prevalence surveys (French et
al., 1989).

Analytical epidemiology
Analytical study designs allow testing of epidemiolog-
ic hypotheses by using appropriate comparison groups.
Two types of analytical studies can be distinguished:
cohort studies and case-control studies. In a cohort or
incidence study two groups of patients, initially free of
the outcome (e. g. NI or death), are compared for the
occurrence of the outcome (Freeman, 1999). In con-
trast, the comparison of exposures (e. g. risk factors of
NI) between two groups of patients with manifested
outcomes, is called a case-control study. Both of these
analytical study types are normally of an observation-
al nature, expressing an ethical dilemma: interventions
in hospital hygiene can be potentially harmful (e. g.
exposing patients to NI), or it may be unethical to
withhold proven interventions (e. g. withdrawal of
standard precautions in a control population). There-
fore, hospital epidemiologists often use observational
studies to generate valuable evidence without being
obliged to obtain data from randomised trials.
What can these analytical studies contribute to the
knowledge about NI? Firstly, they can measure the im-
pact of NIs and quantify the attributable morbidity,
mortality and costs of NI (Harbarth and Pittet, 1996).
Secondly, they help identify risk factors of endemic or
epidemic NI, so that protective measures can be in-
stalled. Villers et al. (Villers et al., 1998) recently illus-
trated the complex relation between utilisation of fluo-
roquinolones and the occurrence of Acinetobacter
baumannii infections in a French intensive care unit
(ICU). We recently published the results of an Entero-
bacter cloacae outbreak investigation in a neonatal
ICU, suggesting that overcrowding and understaffing
in a period of increased workload resulted in this out-
break (Harbarth et al., 1999b). Finally, incidence or
surveillance studies can be used to detect trends or
shifts in pathogens or outcomes of infections. By com-
paring adjusted infection rates to a threshold, valuable
information can be generated for infection control
purposes (Haley, 1995).
A particularly interesting question to consider is the
possible shortcoming of conducting research in hospi-
tal hygiene without using analytical epidemiology: are
the results still the same? Far from providing an abso-
lute statement, the quality of the evidence has often
diminished in those studies designed without scientif-
ically robust analytical epidemiological methods. For
instance, even in the presence of substantial morbidity
or mortality, outbreak investigations were conducted
without the crucial step of performing a case-control
study, resulting in either erroneous or imprecise state-
ments. In an outbreak involving 11 immunocomprom-
ised patients who developed nosocomial sepsis due to
Listeria monocytogenes, the results of a case-control
Epidemiology to prevent nosocomial infections 155
study could have added valuable information for the
prevention of future hospital outbreaks (Elsner et al.,
1997). As another example, crude mortality data
about the impact of NI in 66,000 German acute care
patients were not adjusted for severity of illness, thus
generating conclusions of limited validity (Dinkel and
Lebok, 1994).
Most importantly, there are many examples of
environment-focused studies in hospital hygiene that
reveal the missed opportunity of introducing some
controlled, patient-orientated outcome into the study
design. For instance, a remarkably well-performed
longitudinal study about the control of Legionella
pneumophila in a hospital water system could have
gained clinical importance and generalizability if sur-
veillance data regarding the rate of hospital-acquired
legionellosis had been added (Rohr et al., 1999). Con-
sidering another recently published study, it remains
unclear why routine hygienic monitoring of environ-
mental surroundings in ambulatory surgery units is
necessary to prevent surgical site infections (Christian-
sen et al., 1999). Thus, the final results of these envi-
ronmental studies – although often important and cor-
rect in many respects – are left open to subjective a
posteriori interpretation regarding their impact on
patient care.
Interventional epidemiology
Interventional epidemiology mainly consists of ran-
domised clinical trials, which are one of the key com-
ponents of evidence-based interventions in infection
control. The strength of a clinical trial lies in the ran-
dom allocation of patients to treatment groups; thus,
this study design most closely resembles controlled ex-
perimentation done in laboratory research. Although
expensive and time-consuming to perform, clinical
trials have greatly contributed to the advances of the
prevention of NI. Important examples are the follow-
ing: (1) Prevention of catheter-related bloodstream in-
fections (Darouiche et al., 1999; Maki et al., 1991); (2)
prevention of ventilator-associated pneumonia (Kollef,
1999); (3) prevention of surgical site infections (Del-
linger et al., 1994; Kurz et al., 1996); and (4) control
of transmission of multiresistant microorganisms
(Harbarth et al., 1999a).
Pitfalls and limitations
of hospital epidemiology
There are several potential pitfalls in designing and
analysing epidemiologic studies. An inaccurate study
design may hamper the generalizability of the results.
156 S. Harbarth
For instance, matching of patients as a technique for
the control of confounding has great intuitive appeal
and has been widely used in case-control studies. How-
ever, it has a number of scientific disadvantages, in-
cluding selection bias and the inability to evaluate the
effect of the matching factor. Moreover, the principles
that govern the statistical analysis of epidemiologic
studies are not as well understood as they should be.
Consequently, studies often include the application of
multiple hypotheses testing without appropriate multi-
variable modelling, leading to doubtful statistical asso-
ciations without considering possible alternative expla-
nations caused by chance, bias or confounding.
Speaking in more general terms, hospital epidemiol-
ogy as a young science has several important limita-
tions. There is still a large amount of imprecision and
ambiguity in terminology, which often confuses read-
ers. For instance, the use of the terms rates, mortality,
or confounding all suffered from this confusion
(Elandt-Johnson, 1975; Freeman et al., 1988). Fur-
thermore, as stated by J. Freeman (Freeman, 1999),
the hospital epidemiologist is often merely the passive
witness to what happens, in contrast to physicians and
nurses who play an active part in assigning patient ex-
posures in the hospital. Finally, hospital epidemiology
does not protect against fundamental misjudgements
in the prevention of NI. Despite their strong leadership
role in epidemiologic research, academic health care
institutions in the USA are still trailing behind most
European centers, since they have not implemented the
single but most important tool to prevent the spread
of nosocomial pathogens: bedside, alcohol-based, wa-
terless hand disinfection. In the USA, the misconcep-
tion is still predominant that sink-based handwashing
with antimicrobial soap is superior to alcohol-based
hand disinfection. In fact, the latter practice allows
much faster hand hygiene during patient care and
achieves higher compliance rates (Pittet et al., 1999a;
Voss and Widmer, 1997). Although alcohol-based
hand antisepsis has been shown to be superior to
handwashing in all important microbiological and
technical aspects (Rotter, 1999), the use of alcohol-
based hand antisepsis remains very limited in US hos-
pitals. This is somewhat ironic given that the original
observations of Semmelweis were actually related to
hand disinfection rather than handwashing with soap
and water (Walter, 1976)!
Conclusions
In this article, we reviewed some theoretical and prac-
tical epidemiologic data, which provide important evi-
dence of the benefits of epidemiologic methods, used as
a tool to modify established clinical practice, and to ad-
vance new hypotheses and techniques for the preven-
tion of NI. Since NI have causal and preventive factors
that can be usually identified through systematic inves-
tigation of different populations, epidemiology may
contribute substantially to the understanding of the ef-
fectiveness of hospital hygiene. However, although it is
blindingly obvious as in any scientific research, the
fundamental issue in epidemiology still remains to ask
the right questions and then select the right methods to
answer them. When used adequately, the availability of
systematic epidemiologic methods for the use in hospi-
tal hygiene represents a major opportunity for the
more complete and effective prevention and under-
standing of NI in the next millennium.
Acknowledgements. With great admiration and a deep sense
of loss, this paper is dedicated to the memory of Jonathan
Freeman, who unexpectedly passed away in May 2000. This
work was supported by a research fellowship from the Max-
Kade Foundation, NY. In addition, we would like to thank
Sinclair Wynchank, PhD, for careful reading of the manu-
script.
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