# 02 - 124 Approach to the Patient with an Infectious Disease

### 124 Approach to the Patient with an Infectious Disease

Section 1	 Basic Considerations in 
Infectious Diseases
Neeraj K. Surana, Dennis L. Kasper

Approach to the Patient 

with an Infectious Disease
■
■HISTORIC PERSPECTIVE
The origins of the field of infectious diseases are humble. The notion 
that communicable diseases were due to a miasma (“bad air”) can be 
traced back to at least the mid-sixteenth century. Not until the work of 
Louis Pasteur and Robert Koch in the late nineteenth century was there 
credible evidence supporting the germ theory of disease—i.e., that 
microorganisms are the direct cause of infections. In contrast to this 
relatively slow start, the twentieth century saw remarkable advances in 
the field of infectious diseases, and the etiologic agents of numerous 
infectious diseases were soon identified. Furthermore, the discovery of 
antibiotics and the advent of vaccines against some of the most deadly 
and debilitating infections greatly altered the landscape of human 
health. Indeed, the twentieth century saw the elimination of smallpox, 
one of the great scourges in the history of humanity. These remarkable 
successes prompted Sir Frank MacFarlane Burnet, a noted immunolo­
gist and Nobel laureate, to write in a 1962 publication entitled Natural 
History of Infectious Diseases: “In many ways one can think of the 
middle of the twentieth century as the end of one of the most impor­
tant social revolutions in history, the virtual elimination of infectious 
disease.” Professor Burnet was not alone in this view. Robert Peters­
dorf, a renowned infectious disease expert and former editor of this 
textbook, wrote in 1978 that “even with my great personal loyalties to 
infectious diseases, I cannot conceive a need for 309 more [graduating 
trainees in infectious diseases] unless they spend their time culturing 
each other.” Given the enormous growth of interest in the microbiome 
in the past 20 years, Dr. Petersdorf’s statement might have been ironi­
cally clairvoyant, although he could have had no idea what was in store 
for humanity, with an onslaught of new, emerging, and reemerging 
infectious diseases.
Clearly, even with all the advances of the twentieth century, 
infectious diseases continue to represent a formidable challenge for 
patients and physicians alike. Furthermore, during the latter half of 
the century, several chronic diseases were demonstrated to be directly 
or indirectly caused by infectious microbes; perhaps the most notable 
examples are the associations of Helicobacter pylori with peptic ulcer 
disease and gastric carcinoma, human papillomavirus with cervi­
cal cancer, and hepatitis B and C viruses with liver cancer. In fact, 
~16% of all malignancies are now known to be associated with an 
infectious cause. In addition, numerous emerging and reemerging 
infectious diseases continue to have a dire impact on global health: 
HIV/AIDS, SARS-CoV-2, Ebola, and mpox are but a few examples. 
The fear of weaponizing pathogens for bioterrorism is ever present 
and poses a potentially enormous threat to public health. Moreover, 
escalating antimicrobial resistance in clinically relevant microbes 
(e.g., carbapenem-resistant Enterobacteriaceae and Acinetobacter 
spp., Candida auris, drug-resistant Mycobacterium tuberculosis, and 
vancomycin-resistant enterococci) signifies that the administration 
of antimicrobial agents—once thought to be a panacea—requires 
appropriate stewardship. For all these reasons, infectious diseases 
continue to exert grim effects on individual patients as well as on 
international public health. Even with all the successes of the past 
century, physicians must be as thoughtful about infectious diseases 
now as they were at the beginning of the twentieth century.

Infectious Diseases
PART 5
■
■GLOBAL CONSIDERATIONS
Infectious diseases remain the second leading cause of death world­
wide. Although the rate of infectious disease–related deaths has 
decreased dramatically over the past 25 years, there were still 9.6 mil­
lion such deaths in 2019 (Fig. 124-1A). These deaths disproportion­
ately affect children <1 year of age, adults older than 70 years, and persons 
living in low- and middle-income countries (Fig. 124-1B and 124-1C; 
Chap. 487); in 2019, ~17% of all deaths worldwide were related to 
infectious diseases, with a rate as high as ~69% in sub-Saharan Africa.
Given that infectious diseases are still a major cause of global mortal­
ity, understanding the local epidemiology of disease is critically impor­
tant in evaluating patients. Diseases such as HIV/AIDS have decimated 
southern Africa, with HIV-infected adults representing 16–20% of the 
total population in countries like South Africa, Botswana, and Lesotho, 
and more than 25% in Eswatini. Moreover, drug-resistant tuberculosis is 
rampant throughout the former Soviet-bloc countries, India, China, and 
South Africa. The ready availability of this type of information allows 
physicians to develop appropriate differential diagnoses and treatment 
plans for individual patients. Programs such as the Global Burden of 
Disease seek to quantify human losses (e.g., deaths, disability-adjusted 
life-years) due to diseases by age, sex, and country over time; these data 
not only help inform local, national, and international health policy but 
can also help guide local medical decision-making.
Even though some diseases (e.g., pandemic influenza, mpox) are 
seemingly geographically restricted, the increasing ease of rapid 
worldwide travel has raised concern about their swift spread around 
the globe. Indeed, human migration has historically been the source of 
epidemics: Yersinia pestis spread along trade routes in the fourteenth 
century, Native American populations were devastated by diseases 
such as smallpox and Salmonella that were imported by European 
explorers in the fifteenth and sixteenth centuries, military maneu­
vers helped facilitate the spread of the 1918 influenza pandemic, and 
religious pilgrimages (e.g., the Hajj) provide the means for worldwide 
dissemination of diseases. The continued effects of global travel on 
the spread of infectious diseases are perhaps best highlighted by the 
SARS-CoV-2 pandemic (Chap. 204). Although this virus was first 
identified in Wuhan, China, it quickly spread across the globe and 
brought an abrupt end to virtually all travel and commerce throughout 
the world, plunging economies into a deep recession, resulting at one 
point in more than half the world’s population living under stay-athome orders, and causing the death of ~7 million people worldwide. 
Not only can travelers carry person-to-person transmitted infections 
(e.g., SARS-CoV-2, HIV) anywhere in the world, but they can also 
introduce vector-borne infections to new geographic areas (e.g., chi­
kungunya and Zika viruses) and contribute to the worldwide spread of 
multidrug-resistant organisms. The world’s increasing interconnected­
ness has profound implications not only for the global economy but 
also for medicine and the spread of infectious diseases.
■
■UNDERSTANDING THE MICROBIOTA
Normal, healthy humans are colonized with ~40 trillion bacteria as well 
as countless viruses, fungi, and archaea; taken together, these microor­
ganisms outnumber human cells by ~10 times in the human body 
(Chap. 484). The major reservoir of these microbes is the gastrointesti­
nal tract, but substantial numbers of microbes live in the female genital 
tract, the oral cavity, and the nasopharynx. There is increasing interest in 
the skin and lungs as sites where microbial colonization might be highly 
relevant to the biology and disease susceptibility of the host. These com­
mensal organisms provide the host with myriad benefits, from aiding in 
metabolism to shaping the immune system. With regard to infectious 
diseases, the vast majority of infections are caused by organisms that are 
part of the normal microbiota (e.g., Staphylococcus aureus, Streptococcus 
pneumoniae, Pseudomonas aeruginosa), with relatively few infections 
due to organisms that are strictly pathogens (e.g., Neisseria gonorrhoeae, 
rabies virus). Perhaps it is not surprising that a general understanding

Number of deaths (in millions)

A

PART 5
Infectious Diseases
0.1
C
0.2
0.3
0.4
0.5
0.6
FIGURE 124-1  Magnitude of infectious disease–related deaths globally. A. The absolute number (blue line; left axis) and rate (red line; right axis) of infectious disease–
related deaths throughout the world since 1990. B. Age-specific rates of infectious disease–related deaths in 2019. In both A and B, the charts depict the mean estimate 
and 95% uncertainty intervals. C. A map depicting country-specific data for the percent of total deaths that were attributable to communicable, maternal, neonatal, and 
nutritional disorders in 2019. (Source: Institute for Health Metrics and Evaluation. Used with permission. All rights reserved.)
of the microbiota is essential in the evaluation of infectious diseases. 
Individuals’ microbiotas have a major impact on their susceptibility to 
infectious diseases and even their responses to vaccines. Site-specific 
knowledge of the indigenous microbiota may facilitate appropriate 
interpretation of culture results, aid in selection of empirical antimicro­
bial therapy based on the likely causative agents, and provide additional 
impetus for rational antibiotic use to minimize the untoward effects of 
these drugs on the “beneficial” microbes that inhabit the body.
■
■WHEN TO CONSIDER AN INFECTIOUS ETIOLOGY
The title of this chapter may appear to presuppose that the physician 
knows when a patient has an infectious disease. In reality, this chapter 
can serve only as a guide to the evaluation of a patient in whom an 
infectious disease is a possibility. Once a specific diagnosis is made, the 
reader should consult the subsequent chapters that deal with specific 
microorganisms in detail. The challenge for the physician is to recog­
nize which patients may have an infectious disease as opposed to some 
other underlying disorder. This task is greatly complicated by the fact 
that infections have an infinite range of presentations, from acute lifethreatening conditions (e.g., meningococcemia) to chronic diseases 
of varying severity (e.g., H. pylori–associated peptic ulcer disease) to 

Rate of death (per 100,000)

Rate of death (per 100,000)

0–27 days
28–364 days
1–4 years
5–9 years
10–19 years
20–29 years
30–39 years
40–49 years
50–59 years
60–69 years
70–79 years
80–89 years
90+ years
Age
B
no symptoms at all (e.g., latent M. tuberculosis infection). While it is 
impossible to generalize about a presentation that encompasses all 
infections, common findings in the history, physical examination, and 
basic laboratory testing often suggest that the patient either has an 
infectious disease or should be more closely evaluated for one. This 
chapter focuses on these common findings and how they may direct 
the ongoing evaluation of the patient.
APPROACH TO THE PATIENT
Infectious Disease
See also Chap. 127. 
HISTORY
As in all of medicine, a complete and thorough history is paramount 
in the evaluation of a patient with a possible infectious disease. The 
history is critical for developing a focused differential diagnosis and 
for guiding the physical exam and initial diagnostic testing. Although 
a detailing of all the elements of a history is beyond the scope of this 
chapter, specific components relevant to infectious diseases require

particular attention. In general, these aspects focus on two areas: (1) 
an exposure history that may identify microorganisms with which 
the patient may have come into contact and (2) host-specific factors 
that may predispose to the development of an infection. 
Exposure History  •  History of infections or exposure to 
drug-resistant microbes  Information about a patient’s previous 
infections, with the associated microbial susceptibility profiles, is very 
helpful in determining possible etiologic agents. Specifically, know­
ing whether a patient has a history of infection with drug-resistant 
organisms (e.g., methicillin-resistant S. aureus, vancomycin-resistant 
Enterococcus species, enteric organisms that produce an extendedspectrum β-lactamase or carbapenemase) or may have been exposed 
to drug-resistant microbes (e.g., during a recent stay in a hospital, 
nursing home, or long-term acute-care facility) may alter the choice 
of empirical antibiotics. For example, a patient presenting with sepsis 
who is known to have a history of invasive infection with a multi­
drug-resistant isolate of P. aeruginosa should be treated empirically 
with an antimicrobial regimen that will cover this strain. 
Social history 
Although the social history taken by physicians 
is often limited to inquiries about a patient’s alcohol and tobacco 
use, a complete social history can offer a number of clues to the 
underlying diagnosis. Knowing whether the patient has any highrisk behaviors (e.g., unsafe sexual behaviors, intravenous [IV] drug 
use), potential hobby-associated exposures (e.g., avid gardening, 
with possible Sporothrix schenckii exposure), or occupational expo­
sures (e.g., increased risk for M. tuberculosis exposure in funeral 
service workers) can facilitate diagnosis. The importance of the 
social history is exemplified by a case in 2009 in which a laboratory 
researcher died of a Y. pestis infection acquired during his work; 
although this patient had visited both an outpatient clinic and an 
emergency department, his records at both sites failed to include his 
occupation—information that potentially could have led quickly to 
appropriate treatment and infection control measures. 
Dietary habits 
Because certain pathogens are associated with 
specific dietary habits, inquiring about a patient’s diet can provide 
insight into possible exposures. For example, Shiga toxin–producing 
strains of Escherichia coli, and Toxoplasma gondii are associated 
with the consumption of raw or undercooked meat; Salmonella 
typhimurium, Listeria monocytogenes, and Mycobacterium bovis 
with unpasteurized milk; Leptospira species, parasites, and enteric 
bacteria with unpurified water; and Vibrio species, norovirus, hel­
minths, and protozoa with raw seafood. 
Animal exposures 
Because animals are often important vectors 
of infectious diseases, patients should be asked about exposures to 
any animals, including contact with their own pets, visits to petting 
zoos, or random encounters (e.g., home rodent infestation). For 
example, dogs can carry ticks that serve as agents for the transmis­
sion of several infectious diseases, including Lyme disease, Rocky 
Mountain spotted fever, and ehrlichiosis. Cats are associated with 
Bartonella henselae infection, reptiles with Salmonella infection, 
rodents with leptospirosis, and rabbits with tularemia (Chap. 146). 
Travel history 
Attention should be paid to both international 
and domestic travel. Fever in a patient who has recently returned 
from abroad significantly broadens the differential diagnosis 
(Chap. 130) and, as exemplified by the COVID-19 pandemic, can 
help identify the beginnings of international outbreaks. Even a 
remote history of international travel may reflect patients’ exposure 
to infections with pathogens such as M. tuberculosis or Strongyloides 
stercoralis. Similarly, domestic travel may have exposed patients to 
pathogens that are not normally found in their local environment 
and therefore may not routinely be considered in the differential 
diagnosis. For example, a patient who has recently visited California 
or Martha’s Vineyard may have been exposed to Coccidioides immi­
tis or Francisella tularensis, respectively. Beyond simply identifying 
locations that a patient may have visited, the physician needs to 
delve deeper to learn what kinds of activities and behaviors the 

patient engaged in during travel (e.g., the types of food and sources 
of water consumed, freshwater swimming, animal exposures) and 
whether the patient had the necessary immunizations and/or took 
the necessary prophylactic medications prior to travel; these addi­
tional exposures, which the patient may not think to report without 
specific prompting, are as important as exposures during a patient’s 
routine daily living. 
Host-Specific Factors  Because many opportunistic infections (e.g., 
with Pneumocystis jirovecii, Aspergillus species, or JC virus) affect 
primarily immunocompromised patients, it is of vital importance to 
determine the immune status of the patient. Defects in the immune 
system may be due to an underlying disease (e.g., malignancy, HIV 
infection, malnutrition), a medication (e.g., chemotherapy, gluco­
corticoids, monoclonal antibodies to components of the immune 
system), a treatment modality (e.g., total body irradiation, splenec­
tomy), or a primary immunodeficiency. The type of infection for 
which the patient is at increased risk varies with the specific type 
of immune defect. In concert with determining whether a patient is 
immunocompromised for any reason, the physician should review 
the immunization record to ensure that the patient is adequately pro­
tected against vaccine-preventable diseases (Chap. 129). 
PHYSICAL EXAMINATION
Like the history, a thorough physical examination is crucial in 
evaluating patients with an infectious disease. Some elements of the 
physical exam (e.g., skin, lymphatics) that are often performed in 
a cursory manner as a result of the ever-increasing pace of medi­
cal practice may help identify the underlying diagnosis. Moreover, 
serial exams are critical since new findings may appear as the illness 
progresses. A description of all the elements of a physical exam is 
beyond the scope of this chapter, but the following components 
have particular relevance to infectious diseases. 
CHAPTER 124
Vital Signs  Given that elevations in temperature are often a hall­
mark of infection, paying close attention to the temperature may be 
of value in diagnosing an infectious disease (Chap. 20). The idea 
that 37°C (98.6°F) is the normal human body temperature dates to 
the nineteenth century and was initially based on axillary measure­
ments. Rectal temperatures more accurately reflect the core body 
temperature and are 0.4°C (0.7°F) and 0.8°C (1.4°F) higher than 
oral and axillary temperatures, respectively. This idea of a “normal” 
body temperature does not consider the fact that temperatures tend 
to be higher later in the day, in women, and in younger people. 
Moreover, the average body temperature seems to have dropped 
~0.03°C every decade since the early 1800s to a new normal of 
~36.7°C. Although the definition of fever varies greatly throughout 
the medical literature, the most common definition, which is based 
on studies defining fever of unknown origin (Chap. 22), uses a core 
temperature ≥38.3°C (≥101°F). Although fever is very commonly 
associated with infection, it is also documented in many other 
diseases (Chap. 20). For every 1°C (1.8°F) increase in core tempera­
ture, the heart rate typically rises by ~10 beats/min. Table 124-1 
lists infections that are associated with relative bradycardia (Faget’s 
sign), where patients have a lower heart rate than might be expected 
for a given body temperature. Although this pulse–temperature 
dissociation is not highly sensitive or specific for establishing a 
diagnosis, it is potentially useful in low-resource settings given its 
ready availability and simplicity. 
Approach to the Patient with an Infectious Disease 
Lymphatics  There are ~600 lymph nodes throughout the body, 
and infections are an important cause of lymphadenopathy. A 
physical examination should include evaluation of lymph nodes 
in multiple regions (e.g., popliteal, inguinal, epitrochlear, axillary, 
multiple cervical regions), with notation of the location, size (nor­
mal, <1 cm), presence or absence of tenderness, and consistency 
(soft, firm, or rubbery) and of whether the nodes are matted (i.e., 
connected and moving together). Nodes that are small and firm can 
also be described as “shotty,” referring to the size and consistency 
of buckshot pellets. Of note, palpable epitrochlear nodes are always

TABLE 124-1  Causes of Relative Bradycardia
Infectious Causes
Intracellular organisms
 
  Gram-negative bacteria
Salmonella typhi
Francisella tularensis
Brucella spp.
Coxiella burnetii (Q fever)
Leptospira interrogans
Legionella pneumophila
Mycoplasma pneumoniae
  Tick-borne organisms
Rickettsia spp.
Orientia tsutsugamushi (scrub typhus)
Babesia spp.
  Other
Corynebacterium diphtheriae
Plasmodium spp. (malaria)
Viruses/viral infections
Yellow fever virus
Dengue virus
Viral hemorrhagic feversa
Viral myocarditis
Noninfectious Causes
 
Drug fever
Beta blocker use
Central nervous system lesions
Malignant lymphoma
Factitious fever
aPrimarily early in the course of infection with Marburg or Ebola virus.
PART 5
Infectious Diseases
pathologic. Of patients presenting with lymphadenopathy, 75% 
have localized findings, and the remaining 25% have generalized 
lymphadenopathy (i.e., that involving more than one anatomic 
region). Localized lymphadenopathy in the head and neck region 
is found in 55% of patients, inguinal lymphadenopathy in 14%, and 
axillary lymphadenopathy in 5%. Determining whether the patient 
has generalized versus localized lymphadenopathy can help narrow 
the differential diagnosis, as various infections present differently. 
Skin  The fact that many infections have cutaneous manifestations 
gives the skin examination particular importance in the evaluation 
of patients (Chaps. 21, 61, 134, and A1). It is important to perform 
a complete skin exam, with attention to both front and back. Spe­
cific rashes are often extremely helpful in narrowing the differential 
diagnosis of an infection (Chaps. 21 and A1). In numerous anec­
dotal instances, patients in the intensive care unit have had “fever 
of unknown origin” that was actually due to unrecognized pressure 
ulcers. Moreover, close examination of the distal extremities for 
splinter hemorrhages, Janeway lesions, or Osler’s nodes may yield 
evidence of endocarditis or other causes of septic emboli. 
Foreign Bodies  As previously mentioned, many infections are 
caused by members of the indigenous microbiota. These infections 
typically occur when these microbes escape their normal habitat 
and enter a new one. Thus, maintenance of epithelial barriers 
is one of the most important mechanisms in protection against 
infection. However, hospitalization of patients is often associated 
with breaches of these barriers—e.g., due to placement of IV lines, 
surgical drains, or tubes (e.g., endotracheal tubes and Foley cath­
eters) that allow microorganisms to localize in sites to which they 
normally would not have access (Chap. 147). Accordingly, knowing 
what lines, tubes, and drains are in place is helpful in ascertaining 
what body sites might be infected. 
DIAGNOSTIC TESTING
Laboratory and radiologic testing has advanced greatly over the 
past few decades and has become an important component in 
the evaluation of patients. The dramatic increase in the number 

of serologic diagnostics, antigen tests, and molecular diagnostics 
available to the physician has, in fact, revolutionized medical care. 
However, all of these tests should be viewed as adjuncts to the his­
tory and physical examination—not a replacement for them. The 
selection of initial tests should be based directly on the patient’s 
history and physical exam findings. Moreover, diagnostic testing 
should generally be limited to those conditions that are reasonably 
likely and treatable, important in terms of public health consider­
ations, and/or capable of providing a definitive diagnosis that will 
consequently limit other testing. 
White Blood Cell (WBC) Count  Elevations in the WBC count are 
often associated with infection, although many viral infections are 
associated with leukopenia. It is important to assess the WBC dif­
ferential, given that different classes of microbes are associated with 
various leukocyte types. For example, bacteria are associated with 
an increase in polymorphonuclear neutrophils, often with elevated 
levels of earlier developmental forms such as bands; viruses are 
associated with an increase in lymphocytes; and certain parasites 
are associated with an increase in eosinophils. Table 124-2 lists the 
major infectious causes of eosinophilia. 
Inflammatory Markers  The erythrocyte sedimentation rate (ESR) 
and the C-reactive protein (CRP) level are indirect and direct 
measures of the acute-phase response, respectively, that can be 
used to assess a patient’s general level of inflammation. Moreover, 
these markers can be followed serially over time to monitor disease 
progress/resolution. It is noteworthy that the ESR changes relatively 
slowly, and its measurement more often than weekly usually is not 
useful; in contrast, CRP concentrations change rapidly, and daily 
measurements can be useful in the appropriate context. Although 
these markers are sensitive indicators of inflammation, neither is 
very specific. An extremely elevated ESR (>100 mm/h) has a 90% 
predictive value for a serious underlying disease (Table 124-3). 
Work is ongoing to identify other potentially useful inflammatory 
markers (e.g., procalcitonin, serum amyloid A protein); their clini­
cal utility requires further validation. 
Analysis of Cerebrospinal Fluid (CSF)  Assessment of CSF is criti­
cal for patients with suspected meningitis or encephalitis. An open­
ing pressure should always be recorded, and fluid should routinely 
be sent for cell counts, Gram’s stain and culture, and determination 
of glucose and protein levels. A CSF Gram’s stain typically requires 
>105 bacteria/mL for reliable positivity; its specificity approaches 
100%. Table 124-4 lists the typical CSF profiles for various infec­
tions. In general, CSF with lymphocytic pleocytosis and a low 
glucose concentration suggests either infection (e.g., with Listeria, 
M. tuberculosis, or a fungus) or a noninfectious disorder (e.g., neo­
plastic meningitis, sarcoidosis). Bacterial antigen tests of CSF (e.g., 
latex agglutination tests for Haemophilus influenzae type b, group 
B Streptococcus, S. pneumoniae, and Neisseria meningitidis) are not 
recommended for screening, given that these tests are no more 
sensitive than Gram’s stain; however, these assays can be helpful in 
presumptively identifying organisms seen on Gram’s stain. In con­
trast, other antigen tests (e.g., for Cryptococcus) and some CSF sero­
logic testing (e.g., for Treponema pallidum, Coccidioides) are highly 
sensitive and are useful for select patients. In addition, polymerase 
chain reaction (PCR) analysis of CSF is increasingly being used 
for the diagnosis of bacterial (e.g., N. meningitidis, S. pneumoniae, 
mycobacteria) and viral (e.g., herpes simplex virus, enterovirus) 
infections; while these molecular tests permit rapid diagnosis with 
a high degree of sensitivity and specificity, they often do not allow 
determination of antimicrobial resistance profiles. 
Cultures  The mainstays of infectious disease diagnosis include 
the culture of infected tissue (e.g., surgical specimens) or fluid (e.g., 
blood, urine, sputum, pus from a wound). Samples can be sent for 
culture of bacteria (aerobic or anaerobic), fungi, or viruses. Ideally, 
specimens are collected before the administration of antimicrobial 
therapy; in instances where this order of events is not clinically

TABLE 124-2  Major Infectious Causes of Eosinophiliaa
ORGAN INVOLVED
ORGANISM
EXPOSURE
GEOGRAPHIC DISTRIBUTION
DEGREE OF EOSINOPHILIAb
Central nervous system
Angiostrongylus
Raw seafood
Asia
Mild
Gnathostoma
Raw poultry and seafood
Asia
Moderate to extreme
Eye
Loa loa
Insect bite
Africa
Moderate (expatriates), mild (patients 
living in endemic areas)
Onchocerca
Insect bite
Africa
Mild (expatriates), moderate (patients 
living in endemic areas)
Lung
Chlamydia trachomatis
Sexual transmission
Worldwide
Mild
Strongyloides
Soil
Tropical
Moderate (acute), mild (chronic)
Toxocara canis/Toxocara catic
Dogs, soil
Worldwide
Moderate to extreme
Paragonimus
Crabs and crayfish
Asia
Moderate (acute), mild (chronic)
Coccidioides immitis
Soil
Southwestern United States
Mild (acute), extreme (disseminated)
Brugia malayi
Insect bite
Asia
Mild to moderate
Pneumocystis jirovecii
Air
Worldwide
Mild
Liver
Schistosoma japonicum
Freshwater swimming
Asia
Moderate (acute), mild (chronic)
Schistosoma mansoni
Freshwater swimming
Africa, Middle East, Latin 
America
Fasciola
Watercress
Worldwide
Moderate
Clonorchis
Raw seafood
Asia
Mild to moderate
Opisthorchis
Raw seafood
Asia
Mild to moderate
Intestines
Ascarisd
Raw fruits and vegetables, 
contaminated water
Hookworm
Soil
Worldwide
Mild to moderate
Trichuris
Raw fruits and vegetables, 
contaminated water
Cystoisospora belli
Contaminated water and food
Worldwide
Mild
Dientamoeba fragilis
Unclear; spread via fecal–oral 
route
Capillaria
Raw seafood
Asia
Extreme
Heterophyes
Raw seafood
Asia, Middle East
Mild
Anisakis
Raw seafood
Worldwide
Mild
Baylisascaris procyonise
Soil
North America
Moderate to extreme
Hymenolepis nana
Contaminated water, soil
Worldwide
Mild
Bladder
Schistosoma haematobium
Freshwater swimming
Africa, Middle East
Moderate (acute), mild (chronic)
Muscle
Trichinella
Pork
Worldwide
Moderate to extreme
Lymphatics
Wuchereria bancroftid
Insect bite
Tropical
Moderate to extremef
Bartonella henselae
Cats
Worldwide
Mild
Other
Recovery from bacterial or viral 
infections
—
—
Mild
HIV
Contaminated bodily fluid
Worldwide
Mild
Cryptococcus neoformans
Soil
Worldwide
Moderate to extreme (disseminated)
aThere are numerous noninfectious causes of eosinophilia, such as atopic disease, DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome, and 
pernicious anemia, which can cause mild eosinophilia; drug hypersensitivity and serum sickness, which can cause mild to moderate eosinophilia; collagen vascular 
disease, which can cause moderate eosinophilia; and malignancy, Churg-Strauss syndrome, and hyper-IgE syndromes, which can cause moderate to extreme eosinophilia. 
bMild: 500–1500 cells/μL; moderate: 1500–5000 cells/μL; extreme: >5000 cells/μL. cCan also affect the liver and the eyes. dCan also affect the lungs. eCan also affect the eyes 
and the central nervous system. fLevels are typically higher with pulmonary infections.
feasible, microscopic examination of the specimen (e.g., Gram-stained 
or potassium hydroxide [KOH]–treated preparations) is particularly 
important. Culture of the organism(s) allows identification of the 
etiologic agent(s), determination of the antimicrobial susceptibil­
ity profile, and—when there is concern about an outbreak—isolate 
typing. While cultures are extremely useful in the evaluation of 
patients, determining whether culture results are clinically meaning­
ful or represent contamination (e.g., a non-aureus, non-lugdunensis 
staphylococcal species growing in a blood culture) can sometimes be 
challenging and requires an understanding of the patient’s immune 
status, exposure history, and microbiota. In some cases, serial cultures 
to demonstrate clearance of the organism may be helpful. 
Pathogen-Specific Testing  Numerous pathogen-specific tests 
(e.g., serology, antigen testing, PCR testing) are commercially 

Moderate (acute), mild (chronic)
Worldwide
Mild to extreme
Tropical
Mild
CHAPTER 124
Worldwide
Mild
Approach to the Patient with an Infectious Disease 
available, and many hospitals now offer some of these tests in-house 
to facilitate rapid turnaround that ultimately enhances patient care. 
The reader is directed to relevant chapters on the pathogens of 
interest for specific details. Some of these tests (e.g., universal PCRs, 
shotgun metagenomic sequencing) identify organisms that currently 
are not easily cultivable and have unclear relationships to disease, 
thereby complicating diagnosis. As these tests become more com­
monplace, the relevance of some of these previously unrecognized 
bacteria to human health will likely become more apparent. 
Radiology  Imaging provides an important adjunct to the physical 
examination, allowing evaluation for lymphadenopathy in regions 
that are not externally accessible (e.g., mediastinum, intraabdomi­
nal sites), assessment of internal organs for evidence of infection, 
and facilitation of image-guided percutaneous sampling of deep 
spaces. The choice of imaging modality (e.g., CT, MRI, ultrasound,

TABLE 124-3  Causes of an Extremely Elevated Erythrocyte 
Sedimentation Rate (>100 mm/h)
ETIOLOGIC CATEGORY (% OF CASES)
SPECIFIC CAUSES
Infectious diseases (35–40)
Subacute bacterial endocarditis
Abscesses
Osteomyelitis
Tuberculosis
Urinary tract infection
Inflammatory diseases (15–20)
Giant cell arteritis
Rheumatoid arthritis
Systemic lupus erythematosus
Malignancies (15–20)
Multiple myeloma
Leukemias
Lymphomas
Carcinomas
Other (20–35)
Drug hypersensitivity reactions (drug 
fever)
Ischemic tissue injury/trauma
Renal diseases
nuclear medicine, use of contrast) is best made in consultation with 
a radiologist to ensure that the results will address the physician’s 
specific concerns. 
TREATMENT
Physicians often must balance the need for empirical antibiotic treat­
ment with the patient’s clinical condition. When clinically feasible, it 
is best to obtain relevant samples (e.g., blood, CSF, tissue, purulent 
exudate) for culture prior to the administration of antibiotics, as 
antibiotic treatment often makes subsequent diagnosis more difficult. 
Although a general maxim for antibiotic treatment is to use a regimen 
with as narrow a spectrum as possible (Chap. 149), empirical regi­
mens are necessarily somewhat broad, given that a specific diagnosis 
has not yet been made. Table 124-5 lists empirical antibiotic treatment 
regimens for commonly encountered infectious presentations. These 
regimens should be narrowed as appropriate once a specific diagno­
sis is made. In addition to antibiotics, there is sometimes a role for 
adjunctive therapies, such as intravenous immunoglobulin G (IVIG) 
pooled from healthy adults or hyperimmune globulin prepared from 
PART 5
Infectious Diseases
TABLE 124-4  Typical Cerebrospinal Fluid Profiles for Meningitis and Encephalitisa
BACTERIAL 
MENINGITIS
VIRAL 
MENINGITIS
 
NORMAL
WBC count (per μL)
<5
>1000
25–500
40–600
150–2000
25–100
50–500
Differential of WBC
60–70% 
lymphocytes, 
≤30% monocytes/
macrophages
↑↑PMNs (≥80%)
Predominantly 
lymphocytesc
Lymphocytes or 
PMNs, depending 
on specific 
organism
Gram’s stain
Negative
Positive (in >60% 
of cases)
Negative
Rarely positive
Negative
Occasionally 
positivee
Negative
Glucose (mg/dL)
40–85
<40
Normal
↓ to normal
Normal
<50 in 75% of 
cases
Protein (mg/dL)
15–45
>100
20–80
150–300
50–200
100–200
50–100
Opening pressure 
(mmH2O)
50–180
>300
100–350
160–340
Normal
150–280
Normal to ↑
Common causes
—
Streptococcus 
pneumoniae, 
Neisseria 
meningitidis
Enteroviruses
Candida, 
Cryptococcus, and 
Aspergillus spp.
aNumbers indicate typical results, but actual results may vary. bCerebrospinal fluid characteristics depend greatly on the specific organism. cNeutrophils may predominate 
early in the disease course. dPatients typically have striking eosinophilia as well. eSensitivity can be increased by examination of a smear of protein coagulum (pellicle) and 
the use of acid-fast stains.
Abbreviations: PMNs, polymorphonuclear neutrophils; WBC, white blood cell.

the blood of individuals with high titers of specific antibodies to 
select pathogens (e.g., cytomegalovirus, hepatitis B virus, rabies virus, 
vaccinia virus, Clostridium tetani, varicella-zoster virus, Clostridium 
botulinum toxin). Although the data suggesting efficacy are limited, 
IVIG is sometimes used for patients with suspected staphylococcal or 
streptococcal toxic shock syndrome. 
INFECTION CONTROL
When evaluating a patient with a suspected infectious disease, the 
physician must consider what infection control methods are nec­
essary to prevent transmission of any possible infection to other 
people. In 2007, the U.S. Centers for Disease Control and Prevention 
published guidelines for isolation precautions that are available for 
download at www.cdc.gov/infectioncontrol/guidelines/isolation/. Per­
sons exposed to certain pathogens (e.g., N. meningitidis, HIV, Bacillus 
anthracis) should receive postexposure prophylaxis to prevent disease 
acquisition. (See relevant chapters for details on specific pathogens.) 
WHEN TO OBTAIN AN INFECTIOUS DISEASE CONSULT
At times, primary physicians need assistance with patient manage­
ment from a diagnostic and/or therapeutic perspective. Multiple 
studies have demonstrated that an infectious disease consult is asso­
ciated with improved outcomes, shorter length of hospital stay, and 
decreased costs for patients with various diseases. For example, in a 
prospective cohort study of patients with S. aureus bacteremia, infec­
tious disease consultation was independently associated with a 56% 
reduction in 28-day mortality. While artificial intelligence–based 
chatbots are beginning to be utilized in healthcare settings, they are 
not yet sophisticated enough to supplant an actual infectious dis­
ease consultation. In addition, infectious disease specialists provide 
other services (e.g., infection control, antimicrobial stewardship, 
management of outpatient antibiotic therapy, occupational exposure 
programs) that have been shown to benefit patients. Whenever 
such assistance would be advantageous to a patient with a possible 
infection, the primary physician should opt for an infectious disease 
consult. Specific situations that might prompt a consult include (1) 
difficult-to-diagnose patients with presumed infections, (2) patients 
who are not responding to treatment as expected, (3) patients with 
a complicated medical history (e.g., organ transplant recipients, 
patients immunosuppressed due to autoimmune or inflammatory 
conditions), and (4) patients with “exotic” diseases (i.e., diseases that 
are not typically seen within the region).
FUNGAL 
MENINGITISb
PARASITIC 
MENINGITIS
TUBERCULOUS 
MENINGITIS
ENCEPHALITIS
Predominantly 
lymphocytesc
Predominantly 
lymphocytesc
↑↑ Eosinophils 
(≥50%)d
Normal
Angiostrongylus 
cantonensis, 
Gnathostoma 
spinigerum, 
Baylisascaris 
procyonis
Mycobacterium 
tuberculosis
Herpesviruses, 
enteroviruses, 
influenza virus, 
rabies virus

TABLE 124-5  Initial Empirical Antibiotic Therapy for Common Infectious Disease Presentationsa
CLINICAL SYNDROME
COMMON ETIOLOGIES
ANTIBIOTIC(S)
COMMENTS
SEE CHAPTER(S)
Septic shock
Staphylococcus aureus, 
Streptococcus pneumoniae, 
enteric gram-negative bacilli
Vancomycin, 15 mg/kg q12hb
plus
A broad-spectrum antipseudomonal β-lactam 
(piperacillin-tazobactam, 4.5 g q6h; imipenem, 

1 g q8h; meropenem, 1 g q8h; or cefepime, 

1–2 g q8–12h)
Meningitis
S. pneumoniae, Neisseria 
meningitidis
Vancomycin, 15 mg/kg q12hb
plus
Ceftriaxone, 2 g q12h
CNS abscess
Streptococcus spp., 
Staphylococcus spp., 
anaerobes, gram-negative 
bacilli
Vancomycin, 15 mg/kg q12hb
plus
Ceftriaxone, 2 g q12h
plus
Metronidazole, 500 mg q8h
Acute endocarditis 
(native valve)
S. aureus, Streptococcus 
spp., coagulase-negative 
staphylococci
Vancomycin, 15 mg/kg q12hb
plus
Cefepime, 2 g q8h
Pneumonia
  CommunityS. pneumoniae, Mycoplasma 
pneumoniae, Haemophilus 
influenzae, Chlamydia 
pneumoniae
No comorbiditiesh:
Azithromycin, 500 mg PO? 1, then 250 mg PO qd 
4 days
With comorbiditiesh:
Levofloxacin, 750 mg PO qd
acquired, outpatient
  Inpatient, non-ICU
Above plus Legionella spp.
A respiratory fluoroquinolone (moxifloxacin, 

400 mg IV/PO qd; gemifloxacin, 320 mg PO qd; or 
levofloxacin, 750 mg IV/PO qd)
or
A β-lactam (cefotaxime, ceftriaxone, or 
ampicillin-sulbactam) plus azithromycin
  Inpatient, ICU
Above plus S. aureus
A β-lactam
plus
Azithromycin or a respiratory fluoroquinolone
  Hospital-acquired 
pneumoniad
S. pneumoniae, H. influenzae, 
S. aureus, gram-negative bacilli 
(e.g., Pseudomonas aeruginosa, 
Klebsiella pneumoniae, 
Acinetobacter spp.)
An antipseudomonal β-lactam (cefepime, 2 g 
q8h; ceftazidime, 2 g q8h; imipenem, 500 mg q6h; 
meropenem, 1 g q8h; or piperacillin-tazobactam, 
4.5 g q6h)
plus
An antipseudomonal fluoroquinolone 
(levofloxacin, 700 mg qd, or ciprofloxacin, 

400 mg q8h) or an aminoglycoside (amikacin, 
15–20 mg/kg q24hc; gentamicin, 5–7 mg/kg q24he; 
or tobramycin, 5–7 mg/kg q24he)
Complicated 
intraabdominal 
infection
  Mild to moderate 
 
Anaerobes (Bacteroides spp., 
Clostridium spp.), 

gram-negative bacilli 
(Escherichia coli), 
Streptococcus spp.
Cefoxitin, 2 g q6h
or
A combination of metronidazole (500 mg q8–12h) 
plus one of the following: cefazolin (1–2 g q8h), 
cefuroxime (1.5 g q8h), ceftriaxone (1–2 g 

q12–24h), cefotaxime (1–2 g q6–8h), 
ciprofloxacin (400 mg q12h), levofloxacin 

(750 mg qd)
severity
High-risk patient or 
high degree of severity
Same as above
A carbapenem (imipenem, 500 mg q6h; 
meropenem, 1 g q8h; doripenem, 500 mg q8h)
or
Piperacillin-tazobactam, 3.375 g q6hf
or
A combination of metronidazole (500 mg q8h) 
plus an antipseudomonal cephalosporin 
(cefepime, 2 g q8h; ceftazidime, 2 g q8h)

If a pseudomonal species 
is likely, a second 
antipseudomonal agent should 
be added.

Dexamethasone (0.15 mg/kg IV 
q6h for 2–4 d) should be added 
for patients with suspected 
or proven pneumococcal 
meningitis, with the first dose 
administered 10–20 min before 
the first dose of antibiotics.
143 and pathogenspecific chapters
—

—

If MRSA is a consideration, add 
vancomycin (15 mg/kg q8–12hb) 
or linezolid (600 mg q12h); 
daptomycin should not be used 
in patients with pneumonia.
131 and pathogenspecific chapters
CHAPTER 124
Approach to the Patient with an Infectious Disease 
If MRSA is a consideration, add 
vancomycin (15 mg/kg q8–12hb) 
or linezolid (600 mg q12h); 
daptomycin should not be used 
in patients with pneumonia.
If MRSA is a consideration, add 
vancomycin (15 mg/kg q12hb)
137, 182, and 

pathogen-specific 
chapters
(Continued)