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Flashcards in Typhoid, Osteomyelitis Deck (124):
1

Salmonella Serotyping is based on the

somatic O antigen (lipopolysaccharide cellwall
components), the surface Vi antigen (restricted to S. typhi and S. paratyphi C), and the flagellar H antigen.

2

Salmonellae are

gram-negative, non-spore-forming, facultatively
anaerobic bacilli that measure 2–3 μm by 0.4–0.6 μm.

Salmonellae, like other
Enterobacteriaceae, produce acid on glucose fermentation, reduce
nitrates, and do not produce cytochrome oxidase

3

all salmonellae except Salmonella gallinarum-pullorum are motile by means of peritrichous flagella,

and all but___ produce gas (H2S) on sugar
fermentation.

S. typhi

4

All Salmonella infections begin with ingestion of organisms, most commonly in contaminated food or water.

The infectious dose ranges
from 200 colony-forming units (CFU) to 106 CFU, and the ingested
dose is an important determinant of incubation period and disease
severity.

5

Conditions that decrease either stomach acidity

(an age of <1 year, antacid ingestion, or achlorhydric disease) or intestinal integrity
(inflammatory bowel disease, prior gastrointestinal surgery, or
alteration of the intestinal flora by antibiotic administration) increase
susceptibility to Salmonella infection

6

Once S. typhi and S. paratyphi reach the small intestine, they
penetrate the mucus layer of the gut and traverse the intestinal layer
through

phagocytic microfold (M) cells that reside within Peyer’s
patches.

These ruffles reach out
and enclose adherent bacteria within large vesicles by bacterialmediated
endocytosis.

7

After crossing the epithelial layer of the small intestine, S. typhi and S. paratyphi, which cause enteric (typhoid) fever, are phagocytosed by macrophages.

These salmonellae survive the antimicrobial environment
of the macrophage by sensing environmental signals that trigger alterations in regulatory systems of the phagocytosed bacteria.

For example, PhoP/PhoQ (the best-characterized regulatory system) triggers
the expression of outer-membrane proteins and mediates modifications in lipopolysaccharide so that the altered bacterial surface can resist microbicidal activities and potentially alter host cell signaling

8

Once phagocytosed, typhoidal salmonellae disseminate throughout the body in macrophages via the lymphatics and colonize

reticuloendothelial tissues (liver, spleen, lymph nodes, and bone marrow).

9

development of___ is likely
to be related to the recruitment of mononuclear cells and the development of a specific acquired cell-mediated immune response to S. typhi colonization.

hepatosplenomegaly

The recruitment of additional mononuclear cells and
lymphocytes to Peyer’s patches during the several weeks after initial
colonization/infection can result in marked enlargement and necrosis of the Peyer’s patches, which may be mediated by bacterial products
that promote cell death as well as the inflammatory response.

10

In contrast to enteric fever, which is characterized by an infiltration of mononuclear cells into the small-bowel mucosa, NTS gastroenteritis
is characterized by

massive polymorphonuclear leukocyte infiltration
into both the large- and small-bowel mucosa

This response appears to depend on the induction of interleukin 8, a strong neutrophil chemotactic factor, which is secreted by intestinal cells as a result of
Salmonella colonization and translocation of bacterial proteins into host cell cytoplasm.

11

An additional important factor in the persistence of nontyphoidal salmonellae
in the intestinal tract and the organisms’ capacity to compete
with endogenous flora is the ability to utilize the sulfur-containing
compound___ for metabolism in a microaerophilic environment.

tetrathionate

In the presence of intestinal inflammation, tetrathionate is
generated from thiosulfate produced by epithelial cells through inflammatory
cell production of reactive oxygen species

12

is a systemic disease characterized by fever
and abdominal pain and caused by dissemination of S. typhi or S. paratyphi.

Enteric (typhoid) fever

The disease was initially called typhoid fever because
of its clinical similarity to typhus. In the early 1800s, typhoid fever
was clearly defined pathologically as a unique illness on the basis of
its association with enlarged Peyer’s patches and mesenteric lymph
nodes.

13

In contrast to other Salmonella serotypes, the etiologic agents
of enteric fever—S. typhi and S. paratyphi serotypes A, B, and
C—

have no known hosts other than humans

Most commonly,
food-borne or waterborne transmission results from fecal contamination
by ill or asymptomatic chronic carriers. Sexual transmission
between male partners has been described. Health care workers occasionally
acquire enteric fever after exposure to infected patients or
during processing of clinical specimens and cultures.

14

In endemic regions, enteric fever is
more common in

urban than rural areas
and among young children and adolescents
than among other age groups

15

Enteric fever is a misnomer, in that the hallmark features of this
disease—fever and abdominal pain—are variable. While fever is documented
at presentation in >75% of cases, abdominal pain is reported in

only 30–40%.

16

The incubation period for S. typhi averages

10–14 days but ranges from 5 to 21 days, depending on the inoculum size and the host’s
health and immune status

17

Typhoid

The most prominent symptom is

prolonged fever (38.8°–40.5°C; 101.8°–104.9°F), which can continue for up to 4 weeks if untreated. S. paratyphi A is thought to cause milder disease than S. typhi, with predominantly gastrointestinal symptoms.

Early physical findings of enteric fever include rash (“rose spots”; 30%), hepatosplenomegaly (3–6%), epistaxis, and relative bradycardia at the peak of high fever (<50%).

18

make up a faint, salmon-colored, blanching, maculopapular
rash located primarily on the trunk and chest. The rash is evident

Rose spots

in ~30% of patients at the end of the first week and resolves without
a trace after 2–5 days. Patients can have two or three crops of lesions,
and Salmonella can be cultured from punch biopsies of these lesions.

19

Salmonella

Gastrointestinal bleeding (10–20%)
and intestinal perforation (1–3%) most commonly occur in

the third
and fourth weeks of illness and result from hyperplasia, ulceration, and
necrosis of the ileocecal Peyer’s patches at the initial site of Salmonella
infiltration

20

Salmonella

Neurologic manifestations occur in 2–40% of patients and
include

meningitis, Guillain-Barré syndrome, neuritis, and neuropsychiatric
symptoms (described as “muttering delirium” or “coma
vigil”), with picking at bedclothes or imaginary objects

21

Up to 10% of untreated patients with typhoid fever excrete S. typhi in the feces for up to 3 months,

and 1–4% develop chronic asymptomatic carriage, shedding S. typhi in either urine or stool for
>1 year.

22

Chronic carriage is more common among

women, infants,
and persons who have biliary abnormalities or concurrent bladder
infection with Schistosoma haematobium

23

The definitive diagnosis of enteric fever requires the isolation of

S. typhi or S. paratyphi from blood, bone marrow, other sterile sites,
rose spots, stool, or intestinal secretions

24

The sensitivity of blood culture
is only 40–80%, probably because of high rates of antibiotic use

in endemic areas and the small number of S. typhi organisms (i.e.,
<15/mL) typically present in the blood. Because almost all S. typhi
organisms in blood are associated with the mononuclear cell/platelet
fraction, centrifugation of blood and culture of the buffy coat can
substantially reduce the time to isolation of the organism but do not
increase sensitivity.

25

Bone marrow culture is 55–90% sensitive, and, unlike that of blood culture, its yield is not reduced by up to 5 days of prior antibiotic therapy.

Culture of intestinal secretions (best obtained by a noninvasive
duodenal string test) can be positive despite a negative bone marrow
culture. If blood, bone marrow, and intestinal secretions are all cultured,
the yield is >90%.

26

Stool cultures, although negative in 60–70% of
cases during the first week,

can become positive during the third week
of infection in untreated patients.

27

Serologic tests, including the classic

Widal test for “febrile agglutinins,” and rapid tests to detect antibodies to outermembrane proteins or O:9 antigen are available for detection of S. typhi in developing countries but have lower positive predictive values than blood culture

More sensitive antigen and nucleic acid
amplification tests have been developed to detect S. typhi and S. paratyphi in blood but are not yet commercially available and
remain impractical in many areas where enteric fever is endemic

28

For treatment of
drug-susceptible typhoid fever,___ are the most effective class of agents, with cure rates of ~98% and relapse and fecal carriage rates of <2%.

fluoroquinolones

29

Patients infected with DCS S. typhi strains should be treated

decrease ciprofloxacin susceptibility

with ceftriaxone, azithromycin, or high-dose ciprofloxacin. A 7-day
course of high-dose fluoroquinolone therapy for DCS enteric fever
has been associated with delayed resolution of fever and high rates
of fecal carriage during convalescence. Thus, for DCS strains, a 10- to
14-day course of high-dose ciprofloxacin is preferred.

30

are effective for treatment
of MDR enteric fever, including that caused by DCS and fluoroquinolone-
resistant strains.

Ceftriaxone, cefotaxime, and (oral) cefixime

31

Against DCS strains, is associated with lower rates of
treatment failure and shorter durations of hospitalization than are
fluoroquinolones

azithromycin

32

typhoid
Antibiotic Therapy for Enteric Fever in Adult s

Empirical Treatment

Ceftriaxonea 2 g/d (IV) 10–14 days
Azithromycinb 1 g/d (PO) 5 days

33

typhoid
Fully Susceptible

Optimal
treatment

Ciprofloxacinc 500 mg bid (PO) or 400 mg q12h (IV) 5–7
Azithromycin 1 g/d (PO) 5

Alternative
treatment

Amoxicillin 1 g tid (PO) or 2 g q6h (IV) 14
Chloramphenicol 25 mg/kg tid (PO or IV) 14–21

Trimethoprim sulfamethoxazole
160/800 mg bid (PO) 7–14

34

Multidrug-Resistant
typhoid

Optimal
treatment

Ceftriaxonea 2 g/d (IV) 10–14

Azithromycin 1 g/d (PO) 5

Alternative
treatment

Ciprofloxacin 500 mg bid (PO) or
400 mg q12h (IV) 5–14

35

Two typhoid vaccines are commercially available:

(1) Ty21a, an
oral live attenuated S. typhi vaccine (given on days 1, 3, 5, and 7, with
a booster every 5 years); and (2) Vi CPS, a parenteral vaccine consisting
of purified Vi polysaccharide from the bacterial capsule (given in
a single dose, with a booster every 2 years).

The old parenteral wholecell
typhoid/paratyphoid A and B vaccine is no longer licensed, largely
because of significant side effects, especially fever

The
minimal age for vaccination is 6 years for Ty21a and 2 years for Vi
CPS.

36

associated with chicken eggs emerged as a major
cause of food-borne disease during the 1980s and 1990s.

S. enteritidis infection

37

Gastroenteritis caused by NTS is usually self-limited.

Diarrhea
resolves within 3–7 days and fever within 72 h. Stool cultures remain
positive for 4–5 weeks after infection and—in rare cases of chronic
carriage (<1%)—for >1 year.

38

Antibiotic Therapy for Nontyphoidal Salmonella
Infectio n in Adult s

Preemptive Treatment

Ciprofloxacinb 500 mg bid (PO) 2–3

39

The diagnosis of NTS infection is based on

isolation of the organism
from freshly passed stool or from blood or another ordinarily sterile
body fluid.

40

If the patient has endocarditis or arteritis,

treatment for 6 weeks
with an IV β-lactam antibiotic (such as ceftriaxone or ampicillin) is
indicated.

41

In children circulating microorganisms seed mainly long
bones, whereas in adults the___ is the most commonly
affected site.

vertebral column

42

classifies osteomyelitis according to
anatomic site, comorbidity, and radiographic findings, with stratification
of long-bone osteomyelitis to optimize surgical management; this
system encompasses both systemic and local factors affecting immune
status, metabolism, and local vascularity

Cierny-Mader staging system

43

Any of three mechanisms can underlie osteomyelitis:

(1) hematogenous
spread; (2) spread from a contiguous site following surgery;
and (3) secondary infection in the setting of vascular insufficiency or
concomitant neuropathy

44

The most common primary foci of infection
are the

urinary tract, skin/soft tissue, intravascular catheterization sites, and the endocardium.

45

Wound infection leading
to osteomyelitis typically occurs after

cardiovascular intervention
involving the sternum, orthopedic repair, or prosthetic joint insertion

46

most often follows chronic, progressively deep skin and soft tissue infection of the foot.

Osteomyelitis secondary to vascular insufficiency or peripheral neuropathy

The most common underlying condition
is diabetes.

47

___is caused by skin, soft tissue, and bone ischemia combined with
motor, sensory, and autonomic neuropathy

In diabetes that is poorly controlled, the diabetic foot syndrome

48

Whereas acute
osteomyelitis can generally be treated with antibiotics alone, antibiotic
treatment for chronic osteomyelitis should be combined with

debridement
surgery.

49

Acute hematogenous or contiguous osteomyelitis
evolves over a short period—i.e., a few days or weeks. In contrast,
subacute or chronic osteomyelitis lasts

for weeks or months before
treatment is started.

50

Typical examples of a subacute course are

vertebral
osteomyelitis due to tuberculosis or brucellosis and delayed implantassociated
infections caused mainly by low-virulence microorganisms
(coagulase-negative staphylococci, Propionibacterium acnes

51

develops when insufficient therapy leads to persistence
or recurrence, most often after sternal, mandibular, or foot infection.

Chronic osteomyelitis

52

Long bones are generally involved after hematogenous seeding in children or contiguous spread following trauma or surgery.

The risk of vertebral
osteomyelitis in adults increases with age.

53

also referred to as disk-space infection, septic
diskitis, spondylodiskitis, or spinal osteomyelitis, is the most common
manifestation of hematogenous bone infection in adults.

Vertebral osteomyelitis,

54

extends from the transverse mesocolon and from the lower
pole of the stomach to line the lower peritoneal cavity.

the greater omentum

55

separating the right and left subphrenic spaces
appears to act as a barrier to the spread of infection; consequently,
it is unusual to find bilateral subphrenic collections.

The
falciform ligament

56

A small amount of serous fluid is normally present in the peritoneal space, with a

protein content (consisting mainly of albumin) of <30
g/L and <300 white blood cells (WBCs, generally mononuclear cells)
per microliter.

In bacterial infections, leukocyte recruitment into the
infected peritoneal cavity consists of an early influx of polymorphonuclear
leukocytes (PMNs) and a prolonged subsequent phase of
mononuclear cell migration.

57

In adults, primary
bacterial peritonitis (PBP) occurs most commonly in conjunction with

cirrhosis of the liver (frequently the result of alcoholism).

However, the
disease has been reported in adults with metastatic malignant disease,
postnecrotic cirrhosis, chronic active hepatitis, acute viral hepatitis,
congestive heart failure, systemic lupus erythematosus, and lymphedema
as well as in patients with no underlying disease

58

The presentation of PBP differs from that of secondary peritonitis.
The most common manifestation is

fever, which is reported in up to
80% of patients
Ascites is found but virtually always predates infection.

59

It is vital
to sample the peritoneal fluid of any cirrhotic patient with ascites and
fever. The finding of

>250 PMNs/μL is diagnostic for PBP, according
to Conn

While enteric gramnegative
bacilli such as Escherichia coli are most commonly encountered,
gram-positive organisms such as streptococci, enterococci, or
even pneumococci are sometimes found

60

In PBP, a single organism is typically isolated; anaerobes
are found less frequently in PBP than in secondary peritonitis, in
which a mixed flora including anaerobes is the rule. In fact,

if PBP is
suspected and multiple organisms including anaerobes are recovered
from the peritoneal fluid, the diagnosis must be reconsidered and a
source of secondary peritonitis sought

Contrast-enhanced CT is
useful in identifying an intraabdominal source for infection

61

PBP antibiotics

Third-generation cephalosporins such as cefotaxime (2 g q8h, administered IV) provide reasonable initial coverage in moderately ill patients. Broad-spectrum antibiotics, such as penicillin/ β-lactamase inhibitor combinations (e.g., piperacillin/tazobactam, 3.375 g q6h IV for adults with normal renal function) or ceftriaxone
(2 g q24h IV), are also options

62

A mortality benefit from

albumin (1.5 g/ kg of body weight within 6 h of detection and 1.0 g/kg on day 3) has been demonstrated for patients who present with serum creatinine levels ≥1 mg/dL, blood urea nitrogen levels ≥30 mg/dL, or total bilirubin levels ≥4 mg/dL but not for patients who do not meet these criteria.

63

The normal flora of the colon below the ligament of Treitz contains

10^11 anaerobic organisms/g of feces but only 10^8 aerobes/g; therefore, anaerobic species account for 99.9% of the bacteria.

Leakage of colonic contents (pH 7–8) does not cause significant chemical peritonitis, but infection is intense because of the heavy bacterial load

64

2ndary Bacterial Peritonitis

Antibiotics

penicillin/β-lactamase inhibitor combinations (e.g., ticarcillin/clavulanate, 3.1 g q4–6h IV),

cefoxitin (2 g q4–6h IV), or a combination of either a fluoroquinolone (e.g., levofloxacin, 750 mg q24h IV) or
a third-generation cephalosporin (e.g., ceftriaxone, 2 g q24h IV) plus metronidazole (500 mg q8h IV). Patients in intensive care units should receive imipenem (500 mg q6h IV), meropenem (1 g q8h IV), or combinations of drugs, such as ampicillin plus metronidazole plus
ciprofloxacin. The role of enterococci and Candida species in mixed infections is controversial

65

A third type of peritonitis arises in patients who are undergoing continuous ambulatory peritoneal dialysis (CAPD).

Unlike PBP and
secondary peritonitis, which are caused by endogenous bacteria, CAPD-associated peritonitis usually involves skin organisms

66

The clinical presentation of CAPD peritonitis resembles that of secondary peritonitis in that diffuse pain and peritoneal signs are common.

The dialysate is usually cloudy and contains >100 WBCs/μL, >50% of which are neutrophils

As the normal peritoneum
has very few PMNs, a proportion above 50% is strong evidence of
peritonitis even if the absolute WBC count does not reach 100/μL

Meanwhile, patients undergoing automated peritoneal dialysis without a daytime exchange who present with abdominal pain may have no fluid to withdraw, in which case 1 L of dialysate should be infused and permitted to dwell a minimum of 1–2 h, then drained, examined
for turbidity, and sent for cell count with differential and culture. The differential (with a shortened dwell time) may be more useful than the absolute WBC count.

In equivocal cases or in patients with systemic
or abdominal symptoms in whom the effluent appears clear, a second exchange is performed, with a dwell time of at least 2 h. Clinical judgment should guide initiation of therapy.

67

CAPD Peritonitis

The most common organisms are Staphylococcus species, which accounted for ~45% of cases in one series.

Historically, coagulase negative staphylococcal species were identified most commonly in
these infections, but these isolates have more recently been decreasing in frequency. Staphylococcus aureus is more often involved among patients who are nasal carriers of the organism than among those who
are not, and this organism is the most common pathogen in overt exitsite infections.

68

CAPD peritonitis

In some centers, a first-generation cephalosporin
such as cefazolin (for gram-positive bacteria) and a fluoroquinolone
or a third-generation cephalosporin such as ceftazidime
(for gram-negative bacteria) may be reasonable; in areas with high
rates of infection with methicillin-resistant S. aureus, vancomycin
should be used instead of cefazolin, and gram-negative coverage
may need to be broadened—e.g., with an aminoglycoside, ceftazidime,
cefepime, or carbapenem. Broad coverage including vancomycin
should be particularly considered for toxic patients and for
those with exit-site infections. Vancomycin should also be included
in the regimen if the patient has a history of colonization or infection
with methicillin-resistant S. aureus or has a history of severe allergy
to penicillins and cephalosporins.

69

CAPD peritonitis

Loading doses are administered
intraperitoneally; doses depend on the dialysis method and the
patient’s renal function. Antibiotics are given either continuously
(i.e., with each exchange) or intermittently (i.e., once daily, with the
dose allowed to remain in the peritoneal cavity for at least 6 h). If the
patient is severely ill, IV antibiotics should be added at doses appropriate
for the patient’s degree of renal failure. The clinical response
to an empirical treatment regimen should be rapid; if the patient has
not responded after 48–96 h of treatment, new samples should be
collected for cell counts and cultures, and catheter removal should
be considered. For patients who lack exit-site or tunnel infection, the
typical duration of antibiotic treatment is 14 days.

70

This organism, although accounting for only 0.5% of
the normal colonic flora, is the anaerobe most frequently isolated from
intraabdominal infections, is especially prominent in abscesses, and is
the most common anaerobic bloodstream isolate

B. fragilis.

Of the several virulence factors identified in B. fragilis, one is
critical: the capsular polysaccharide complex found on the bacterial
surface. This complex comprises at least eight distinct surface polysaccharides.
Structural analysis of these polysaccharides has shown an
unusual motif of oppositely charged sugars. Polysaccharides having
these zwitterionic characteristics, such as polysaccharide A, evoke
a host response in the peritoneal cavity that localizes bacteria into
abscesses.

71

Of all intraabdominal abscesses, 74% are intraperitoneal
or retroperitoneal and are not visceral.

Most intraperitoneal
abscesses result from fecal spillage from a colonic source, such as an
inflamed appendix. Abscesses can also arise from other processes.
They usually form within weeks of the development of peritonitis and
may be found in a variety of locations from omentum to mesentery,
pelvis to psoas muscles, and subphrenic space to a visceral organ such
as the liver, where they may develop either on the surface of the organ
or within it.

72



is frequently used
for this purpose because it reaches high tissue levels in the pancreas
(although it is not unique in this regard).

Imipenem

73

most common source for a liver abscess. Currently, associated disease
of the

biliary tract is most common. Pylephlebitis (suppurative thrombosis
of the portal vein), usually arising from infection in the pelvis but
sometimes from infection elsewhere in the peritoneal cavity, is another
common source for bacterial seeding of the liver

74

is the most common presenting sign of liver abscess

Fever

75

The single most
reliable laboratory finding is an elevated ____which is documented in 70% of patients with liver
abscesses.

serum concentration of alkaline
phosphatase,

50% of patients have elevated serum levels of bilirubin, and 48% have
elevated concentrations of aspartate aminotransferase. Other laboratory
findings include leukocytosis in 77% of patients, anemia (usually
normochromic, normocytic) in 50%, and hypoalbuminemia in 33%.

76

These communityacquired
infections have been linked to a virulent

hypermucoviscous K.
pneumoniae phenotype and to a specific genotype. The typical syndrome
includes liver abscess, bacteremia, and metastatic infection

Ampicillin/amoxicillin therapy started within the previous 30 days has
been associated with increased risk for this syndrome, presumably
because of selection for the causative strain.

77

Unless previous surgery
has been performed, anaerobes are not generally involved in liver
abscesses arising from biliary infections. In contrast, in liver abscesses
arising from pelvic and other intraperitoneal sources, a mixed flora
including both aerobic and anaerobic species is common

; B. fragilis is
the species most frequently isolated.

With hematogenous spread of
infection, usually only a single organism is encountered; this species
may be S. aureus or a streptococcal species such as one in the
Streptococcus milleri group.

78

Liver
abscesses may also be caused by Candida species; such abscesses usually

follow fungemia in patients receiving chemotherapy for cancer and
often present when PMNs return after a period of neutropenia.

79

is the mainstay of therapy for intraabdominal
abscesses, including liver abscesses; the approach can be either
percutaneous (with a pigtail catheter kept in place or possibly with
a device that can perform pulse lavage to fragment and evacuate
the semisolid contents of a liver abscess) or surgical

Drainage

80

Treatment of candidal liver abscesses often entails initial administration
of amphotericin B or liposomal amphotericin, with subsequent
fluconazole therapy (Chap. 240).

In some cases, therapy
with fluconazole alone (6 mg/kg daily) may be used

81

Splenic Abscess

is the
most common associated infection

Bacterial endocarditis

82

are the most common bacterial isolates from splenic abscesses, followed
by S. aureus—presumably reflecting the associated endocarditis

Streptococcal species

83

Splenic Abscess

\Salmonella species are seen fairly commonly,
especially in patients with

sickle cell hemoglobinopathy.

84

Patients undergoing splenectomy should be vaccinated
against encapsulated organisms

(Streptococcus pneumoniae,
Haemophilus influenzae, Neisseria meningitidis). The most important
factor in successful treatment of splenic abscesses is early diagnosis

85

Before antibiotics became available, most
renal and perinephric abscesses were hematogenous in origin, usually
complicating prolonged bacteremia, with S. aureus most commonly
recovered. Now, in contrast, >75% of perinephric and renal abscesses
arise from

a urinary tract infection

Of the risk
factors that have been associated with the development of perinephric
abscesses, the most important is concomitant nephrolithiasis obstructing
urinary flow. Of patients with perinephric abscess, 20–60% have
renal stones.

86

The organisms most frequently encountered in perinephric and renal abscesses are E. coli, Proteus species, and Klebsiella species.

E. coli, the aerobic species most commonly found in the colonic flora, seems to have unique virulence properties in the urinary tract, including
factors promoting adherence to uroepithelial cells.

87

The urease of
Proteus species splits urea, thereby creating a more alkaline and more
hospitable environment for bacterial proliferation.

Proteus species
are frequently found in association with large struvite stones caused
by the precipitation of magnesium ammonium sulfate in an alkaline
environment. These stones serve as a nidus for recurrent urinary tract
infection.

88

Associated osteomyelitis due to spread from bone to
muscle or from muscle to bone is common in psoas abscesses

S. aureus is most likely to be isolated when a psoas abscess arises from
hematogenous spread or a contiguous focus of osteomyelitis; a mixed
enteric flora is the most likely etiology when the abscess has an intraabdominal
or pelvic source

89

For Shigella, enterohemorrhagic Escherichia coli, Giardia lamblia, or Entamoeba, as few
as 10–100 bacteria or cysts can produce infection, while

10^5−10^8
Vibrio cholerae organisms must be ingested to cause disease

90

Enterotoxigenic E. coli, which causes watery diarrhea, produces an
adherence protein called

colonization factor antigen that is necessary for
colonization of the upper small intestine by the organism prior to the
production of enterotoxin.

91

Enteropathogenic E. coli, an agent of diarrhea
in young children, and

enterohemorrhagic E. coli, which causes hemorrhagic colitis and the hemolytic-uremic syndrome, produce virulence
determinants that allow these organisms to attach to and efface the
brush border of the intestinal epithelium.

92

Noninflammatory
(enterotoxin)

Proximal small
bowel

Watery diarrhea

No fecal leukocytes; mild or no increase in fecal lactoferrin

Vibrio cholerae, enterotoxigenic Escherichia coli (LT and/or ST), enteroaggregative
E. coli, Clostridium perfringens, Bacillus cereus, Staphylococcus
aureus, Aeromonas hydrophila, Plesiomonas shigelloides, rotavirus, norovirus,
enteric adenoviruses, Giardia lamblia, Cryptosporidium spp., Cyclospora
spp., microsporidia

93

Inflammatory (invasion or cytotoxin)

Colon or distal small bowel

Dysentery or inflammatory diarrhea

Fecal polymorphonuclear leukocytes; substantial
increase in fecal lactoferrin

Shigella spp., Salmonella spp., Campylobacter jejuni, enterohemorrhagic
E. coli, enteroinvasive E. coli, Yersinia enterocolitica, Listeria monocytogenes,
Vibrio parahaemolyticus, Clostridium difficile, A. hydrophila, P. shigelloides,
Entamoeba histolytica, Klebsiella oxytoca

94

Penetrating

Distal small bowel

Enteric fever Fecal mononuclear leukocytes

Salmonella typhi, Y. enterocolitica

95

The prototypical enterotoxin is cholera toxin, a heterodimeric protein
composed of one A and five B subunits.

The A subunit contains
the enzymatic activity of the toxin, while the B subunit pentamer
binds holotoxin to the enterocyte surface receptor, the ganglioside
GM1.

After the binding of holotoxin, a fragment of the A subunit is
translocated across the eukaryotic cell membrane into the cytoplasm,
where it catalyzes the adenosine diphosphate ribosylation of a guanosine
triphosphate–binding protein and causes persistent activation
of adenylate cyclase

The end result is an increase of cyclic adenosine
monophosphate in the intestinal mucosa, which increases Cl– secretion
and decreases Na+ absorption, leading to a loss of fluid and the
production of diarrhea.

96

Enterotoxigenic strains of E. coli may produce a protein called heatlabile enterotoxin (LT) that is similar to cholera toxin and causes secretory diarrhea by the same mechanism.

Alternatively, enterotoxigenic strains of E. coli may produce heat-stable enterotoxin (ST), one form of
which causes diarrhea by activation of guanylate cyclase and elevation of intracellular cyclic guanosine monophosphate. Some enterotoxigenic strains of E. coli produce both LT and ST

97

Dysentery may result not only from the production of cytotoxins but
also from

bacterial invasion and destruction of intestinal mucosal cells.
Infections due to Shigella and enteroinvasive E. coli are characterized
by the organisms’ invasion of mucosal epithelial cells, intraepithelial
multiplication, and subsequent spread to adjacent cells

98

Salmonella
causes inflammatory diarrhea by invasion of the bowel mucosa but
generally is not associated with the destruction of enterocytes or the
full clinical syndrome of dysentery.

Salmonella typhi and Yersinia
enterocolitica can penetrate intact intestinal mucosa, multiply intracellularly
in Peyer’s patches and intestinal lymph nodes, and then disseminate
through the bloodstream to cause enteric fever, a syndrome
characterized by fever, headache, relative bradycardia, abdominal pain,
splenomegaly, and leukopenia.

99

is an important barrier to enteric pathogens,
and an increased frequency of infections due to Salmonella, G.
lamblia, and a variety of helminths has been reported among patients
who have undergone gastric surgery or are achlorhydric for some other
reason.

The acidic pH of the stomach

Neutralization of gastric acid with antacids, proton pump inhibitors,
or H2 blockers—a common practice in the management of hospitalized
patients—similarly increases the risk of enteric colonization.

100

Normal peristalsis is the major mechanism for clearance of bacteria
from the proximal small intestine. When intestinal motility is impaired
(e.g., by treatment with opiates or other antimotility drugs, anatomic
abnormalities, or hypomotility states), the frequency of bacterial
overgrowth and infection of the small bowel with enteric pathogens
is increased

Some patients whose treatment for Shigella infection
consists of diphenoxylate hydrochloride with atropine (Lomotil)experience prolonged fever and shedding of organisms,

while patients
treated with opiates for mild Salmonella gastroenteritis have a higher
frequency of bacteremia than those not treated with opiates

101

Mild dehydration is indicated by

thirst, dry mouth, decreased axillary sweat, decreased urine output, and slight weight loss.

102

Signs of moderate dehydration include an

orthostatic fall in blood pressure, skin tenting, and sunken eyes (or, in infants, a sunken fontanelle)

103

Signs of severe dehydration include

lethargy, obtundation, feeble pulse, hypotension, and frank shock.

104

is generally defined as chronic;

Diarrhea lasting >2 weeks

105

(painful rectal spasms with a strong urge to defecate but little passage of stool) may be
a feature of cases with proctitis, as in shigellosis or amebiasis.

Tenesmus

Vomiting implies an acute infection (e.g., a toxin-mediated illness or food poisoning)
but can also be prominent in a variety of systemic illnesses (e.g., malaria) and in intestinal obstruction

106

Grossly bloody
or mucoid stool suggests an inflammatory process.

A test for fecal
leukocytes (preparation of a thin smear of stool on a glass slide,
addition of a drop of methylene blue, and examination of the wet
mount) can suggest inflammatory disease in patients with diarrhea

107

A test for fecal lactoferrin, which is a

marker of fecal leukocytes,

108

is the most common travel-related infectious
illness (Chap. 149). The time of onset is usually 3 days to 2 weeks after
the traveler’s arrival in a resource-poor area; most cases begin within
the first 3–5 days. The illness is generally self-limited, lasting 1–5 days.
The high rate of diarrhea among travelers to underdeveloped areas is
related to the ingestion of contaminated food or water

traveler’s diarrhea

109

Globally, most morbidity and mortality from enteric pathogens
involves children

<5 years of age.

110

Individuals with hypogammaglobulinemia are at particular
risk of C. difficile colitis and giardiasis.

Patients with cancer are more
likely to develop C. difficile

111

1–6 h
incubation period

Staphylococcus aureus
Bacillus cereus

Outbreaks following picnics where potato salad,
mayonnaise, and cream pastries have been served offer classic examples
of staphylococcal food poisoning. Diarrhea, nausea, vomiting, and
abdominal cramping are common, while fever is less so.

112

8–16 h
incubation period

Clostridium perfringens
B. cereus

113

>16 h
incubation period

Vibrio cholerae

Enterotoxigenic
Escherichia coli

Enterohemorrhagic
E. coli

Salmonella spp.

114

B. cereus can produce either a syndrome with a short incubation
period—the emetic form, mediated by a staphylococcal type of enterotoxin—
or one with a longer incubation period (8–16 h)—the diarrheal
form, caused by an enterotoxin resembling E. coli LT, in which diarrhea
and abdominal cramps are characteristic but vomiting is uncommon.

The emetic form of B. cereus food poisoning is associated with
contaminated fried rice; the organism is common in uncooked rice,
and its heat-resistant spores survive boiling. If cooked rice is not refrigerated,
the spores can germinate and produce toxin. Frying before
serving may not destroy the preformed, heat-stable toxin

115

Cholera

thiosulfate–citrate–bile salts–sucrose (TCBS)
or tellurite-taurocholate-gelatin (TTG) agar

116

All patients with fever and evidence of inflammatory disease
acquired outside the hospital should have stool cultured for

Salmonella, Shigella, and Campylobacter

117

Salmonella and Shigella can be selected
on MacConkey agar as non-lactose-fermenting (colorless) colonies or

can be grown on Salmonella-Shigella agar or in selenite enrichment
broth, both of which inhibit most organisms except these pathogens

118

Isolation of C. jejuni
requires inoculation of fresh stool onto selective growth medium
and incubation

at 42°C in a microaerophilic atmosphere

119

“reduced-osmolarity/reduced-salt”
ORS that is better tolerated and more effective than classic ORS. This
preparation contains

2.6 g of sodium chloride,
2.9 g of trisodium citrate,
1.5 g of potassium chloride, and
13.5 g of glucose (or 27 g of sucrose) per liter of water.

120

Watery diarrhea (no blood in stool,
no fever), 1 or 2 unformed stools
per day without distressing enteric
symptoms

Oral fluids (oral rehydration solution,
Pedialyte, Lytren, or flavored mineral
water) and saltine crackers

121

Watery diarrhea (no blood in stool,
no fever), 1 or 2 unformed stools per
day with distressing enteric
symptoms

Bismuth subsalicylate (for adults):
30 mL or 2 tablets (262 mg/tablet)
every 30 min for 8 doses; or
loperamideb: 4 mg initially followed
by 2 mg after passage of each
unformed stool, not to exceed
8 tablets (16 mg) per day
(prescription dose) or 4 caplets
(8 mg) per day (over-the-counter
dose); drugs can be taken for 2 days

122

Watery diarrhea (no blood in stool,
no distressing abdominal pain, no
fever), >2 unformed stools per day

Antibacterial drugc plus (for adults)
loperamideb (see dose above)

123

Dysentery (passage of bloody stools)
or fever (>37.8°C)

Antibacterial drugc

124

Vomiting, minimal diarrhea

Bismuth subsalicylate (for adults; see
dose above)