1208 PART 5 Infectious Diseases

C. minutissimum (Erythrasma) Erythrasma is a cutaneous infection producing reddish-brown, macular, scaly, pruritic intertriginous

patches. The dermatologic presentation under the Wood’s lamp is

of coral red fluorescence. C. minutissimum appears to be a common

cause of erythrasma, although there is evidence for a polymicrobial

etiology in certain settings. This microbe has also been associated

with bacteremia in patients with hematologic malignancy. Erythrasma

responds to topical erythromycin, clarithromycin, clindamycin, or

fusidic acid, although more severe infections may require oral macrolide therapy.

Other Nondiphtherial Corynebacteria C. xerosis is a human

commensal found in the conjunctiva, nasopharynx, and skin. This

nontoxigenic organism is occasionally identified as a source of invasive

infection in immunocompromised or postoperative patients and prosthetic joint recipients. C. amycolatum is a closely related species but

tends to demonstrate more antibiotic resistance. C. striatum is found

in the anterior nares, skin, face, and upper torso of healthy individuals. Also nontoxigenic, this organism has been associated with invasive opportunistic infections in severely ill or immunocompromised

patients. C. glucuronolyticum is a nonlipophilic species that causes

male genitourinary tract infections such as prostatitis and urethritis.

These infections may be successfully treated with a wide variety of

antibacterial agents, including β-lactams, rifampin, aminoglycosides,

or vancomycin; however, the organism appears to be resistant to

fluoroquinolones, macrolides, and tetracyclines. C. imitans has been

identified in eastern Europe as a nontoxigenic cause of pharyngitis.

C. auris has been identified in children with otitis media; it is susceptible to fluoroquinolones, rifampin, tetracycline, and vancomycin

but resistant to penicillin G and variably susceptible to macrolides.

C. pseudodiphtheriticum is a nontoxigenic species that is part of the

normal human flora. Human infections—particularly endocarditis

of either prosthetic or natural valves and invasive pneumonia—have

been reported only rarely. Although C. pseudodiphtheriticum may be

isolated from the nasopharynx of patients with suspected diphtheria,

it is part of the normal flora and does not produce diphtheria toxin. C.

propinquum, a close relative of C. pseudodiphtheriticum, is part of CDC

group D-1 and has been isolated from the human respiratory tract and

blood. C. afermentans and subspecies belongs to CDC group ANF-1;

it is a rare human pathogen that has been isolated from human blood

and abscesses.

Rhodococcus Rhodococcus species are phylogenetically related to

the corynebacteria. These gram-positive coccobacilli have been associated with tuberculosis-like infections in humans with granulomatous

pathology. While R. equi is best known, other near-relative species

have been identified in human infections including R. fascians, R. erythropolis, R. rhodochrous, Gordonia bronchialis, G. sputi, G. terrae, and

Tsukamurella paurometabola.

R. equi has been recognized as a cause of pneumonia in horses since

the 1920s and as a cause of related infections in cattle, sheep, and swine.

It is found in soil as an environmental microbe. The organisms vary in

length; appear as spherical to long, curved, clubbed rods; and produce

large irregular mucoid colonies. R. equi cannot ferment carbohydrates

or liquefy gelatin and is often acid fast. An intracellular pathogen of

macrophages, R. equi can cause granulomatous necrosis and caseation.

This organism has most commonly been identified in pulmonary

infection, but infections of brain, bone, and skin also have been

reported. Most commonly, R. equi disease manifests as nodular and/or

cavitary pneumonia of the upper lobe—a picture similar to that seen in

tuberculosis or nocardiosis. Most patients are immunocompromised,

often by HIV infection. Subcutaneous nodular lesions also have been

identified. The involvement of R. equi should be considered when any

patient presents with a tuberculosis-like syndrome.

Infection due to R. equi has been treated successfully with antibiotics that penetrate intracellularly, including macrolides, clindamycin,

rifampin, and trimethoprim-sulfamethoxazole. β-Lactam antibiotics

have not been useful. The organism is routinely susceptible to vancomycin, which is considered the drug of choice.

Arcanobacteria Arcanobacterium haemolyticum was identified as an

agent of wound infections in U.S. soldiers in the South Pacific during

World War II. It appears to be a human commensal of the nasopharynx

and skin, but it is known to cause true pharyngitis as well as chronic

skin ulcers. In contrast to the much more common pharyngitis caused

by Streptococcus pyogenes, A. haemolyticum pharyngitis is associated

with a scarlatiniform rash on the trunk and proximal extremities in

about half of cases; this illness is occasionally confused with toxic shock

syndrome. Because A. haemolyticum pharyngitis primarily affects

teenagers, it has been postulated that the rash–pharyngitis syndrome

may represent co-pathogenicity, synergy, or opportunistic secondary

infection with Epstein-Barr virus. A. haemolyticum has also been

reported as a cause of bacteremia, soft tissue infections, osteomyelitis,

and cavitary pneumonia, predominantly in the setting of underlying

diabetes mellitus. The organism is susceptible to most β-lactams, macrolides, fluoroquinolones, clindamycin, vancomycin, and doxycycline.

However, resistance to trimethoprim-sulfamethoxazole as well as tetracycline is common.

■ FURTHER READING

Kim R, Reboli AC: Other coryneform bacteria and Rhodococcus, in

Mandell, Douglas, and Bennett’s Principles and Practice of Infectious

Diseases, 9th ed. JE Bennett et al (eds). Philadelphia, Elsevier, 2020,

pp 2532–2542.

Moore LS et al: Corynebacterium ulcerans cutaneous diphtheria. Lancet Infect Dis 15:1100, 2015.

Saleeb PG: Corynebacterium diphtheriae (diphtheria), in Mandell,

Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 9th ed. JE Bennett et al (eds). Philadelphia, Elsevier, 2020,

pp 2526–2531.

Sharma NC et al: Diphtheria. Nat Rev Dis Primers 5:81, 2019.

Wiedermann BL: Diphtheria in the 21st century: New insights and a

wake-up call. Clin Infect Dis 71:98, 2020.

Listeria monocytogenes is a ubiquitous environmental saprophyte

and an intracellular pathogen in several animals. Humans develop

L. monocytogenes infection—listeriosis—primarily through foodborne

transmission. The clinical spectrum of listeriosis ranges from febrile

gastroenteritis in healthy persons to invasive disease, including bacteremia and meningoencephalitis. Typical risk groups for invasive

disease are pregnant women and their neonates, older adults, and

immunocompromised persons.

■ MICROBIOLOGY

L. monocytogenes is a nonsporulating, facultatively anaerobic, short,

gram-positive rod that grows well on blood agar, demonstrating small

zones of β-hemolysis. Organisms sometimes appear gram-variable

and resemble cocci, diplococci, or diphtheroids; this appearance can

obscure the diagnosis. On light microscopy, L. monocytogenes demonstrates characteristic tumbling motility. It grows optimally at 30–37o

C

but can grow at refrigerator temperatures as low as 4o

C. Serotypes are

usually determined on the basis of somatic (O) and flagellar (H) antigens. Nearly all human illness is caused by serotypes 1/2a, 1/2b, and 4b.

■ PATHOGENESIS

L. monocytogenes lives in soil and decaying vegetable matter. Numerous

bird and mammal species are reservoirs. In addition to its ability to

grow at cold temperatures, Listeria’s tolerance to low-pH and high-salt

environments facilitates its environmental survival. Human infection

151 Listeria monocytogenes

Infections

Jennifer P. Collins, Patricia M. Griffin

1209CHAPTER 151 Listeria monocytogenes Infections

thus establishing foodborne transmission. It is now known that

L. monocytogenes transmission is almost always foodborne. Listeriosis

is a nationally notifiable disease in the United States. According to the

Centers for Disease Control and Prevention’s (CDC’s) Foodborne Diseases Active Surveillance Network (FoodNet), the incidence of invasive

listeriosis was 2.4–3.7 cases per million persons during 2008–2019

(Fig. 151-1). Listeriosis is a substantial contributor to deaths from

foodborne illness despite being a relatively uncommon cause of illness.

Only about 3% of cases of listeriosis are part of a recognized

outbreak—i.e., have a source determined; however, outbreak investigations provide data on major food sources. Hot dogs and deli meats

were the major sources of U.S. outbreaks until 2002, when an outbreak

linked to turkey deli meat resulted in eight deaths and the recall of

>30 million pounds of meat. After that outbreak, the U.S. Department

of Agriculture’s Food Safety and Inspection Service issued new regulations and intensified testing for L. monocytogenes in ready-to-eat meat

and poultry plants, and producers added growth inhibitors. Since then,

these products have rarely been implicated in outbreaks, yet the incidence of listeriosis has not declined significantly in about two decades

(Fig. 151-1). Evidence that other sources are now more important is

supported by the marked decline in isolations of L. monocytogenes

from ready-to-eat meats (Fig. 151-1). Dairy products are an important

source, especially soft cheese made with raw (unpasteurized) milk or

produced from pasteurized milk in unsanitary facilities; ice cream and

raw milk also have caused outbreaks. Raw produce is another important source; outbreaks have been traced to packaged salad, sprouts,

cantaloupe and other fruit, caramel apples, and frozen vegetables. A

single strain of L. monocytogenes can survive in a production facility for

years. A small amount of contamination during production can lead

to much higher levels when food is ingested because of the organism’s

ability to grow at refrigerator temperatures.

Most people with invasive listeriosis are older adults, whose risk

increases with each decade over 59 years of age. Most other patients

have impaired cellular immunity associated with hematologic malignancy, solid organ or bone marrow transplantation, HIV infection,

or receipt of glucocorticoid or other immunosuppressive drugs. The

group at highest risk is pregnant women, who almost always have

only mild flulike symptoms but who transmit the infection to the fetus

through the placenta. Some neonates may acquire infection in the

hospital, as illustrated by an outbreak associated with contaminated

mineral oil. Rarely, children and adults with no risk factors develop

invasive listeriosis, probably through heavy contamination of food. The

typically occurs through ingestion of contaminated food. The infectious dose has not been well established but is likely to be very low for

persons with severely impaired cellular immunity. Increased gastric

pH, such as that due to proton pump inhibitors, probably promotes

the organism’s survival in the gastrointestinal tract. After transcytosis

across the intestinal epithelium, the bacteria travel via mesenteric

lymph nodes and the bloodstream to the liver and spleen, its target

organs; dissemination to other organs can occur. L. monocytogenes can

also migrate across the blood–brain barrier and the placenta.

Virulence factors, including a pore-forming cytolysin (listeriolysin O;

LLO) and phospholipases, facilitate evasion of intracellular killing

by mediating escape from the internalization vacuole; the organism can then enter the host cell cytosol. The surface protein ActA

facilitates direct cell-to-cell movement within the cytosol, allowing

L.  monocytogenes to avoid encountering components of the host

immune system, such as antibodies and complement, during dissemination. Iron promotes listerial growth of the organism in vitro, an effect

that explains why listeriosis has been associated with iron-overload

conditions, including hemochromatosis.

■ IMMUNE RESPONSE

Although L. monocytogenes is ubiquitous in the environment, infection

is rare because of both innate and adaptive host immune responses.

Studies of mice have contributed to a detailed understanding of the

immune response to infection. Activation of innate immunity is

important for host survival. Interferon γ and tumor necrosis factor α

(TNF-α) are among the key cytokines involved in this response. T cells

are the primary drivers of the adaptive immune response, furthering

the clearance of infected cells. Cytotoxic (CD8+) T cells are the main

contributors to long-term immunity.

These immune mechanisms explain the association between invasive listeriosis and immunocompromising conditions, particularly

impaired cellular immunity. In light of numerous reports of invasive

listeriosis in patients treated with TNF-α inhibitors, the U.S. Food and

Drug Administration added listeriosis to the boxed warning for this

drug class. Because L. monocytogenes induces a vigorous cell-mediated

immune response, attenuated strains that express foreign antigens are

undergoing clinical trials as a cancer immunotherapy.

■ EPIDEMIOLOGY

More than 50 years after L. monocytogenes was first identified as a

human pathogen, a 1983 outbreak investigation implicated coleslaw,

Year

1988

0

1

2

3

4

1990 1992 1994 1996 1998 2000 2002

5

6

0

1

2

3

4

5

9

8

7

6

2004 2006 2008 2010 2012 2014 2016 2018

2003: New regulations for ready-to-eat meat and poultry plants

2000: Listeriosis made nationally notifiable

1998: PulseNet began subtyping

1989: Case associated with turkey franks; new regulatory policies, industry efforts

Products yielding

L. monocytogenes, %

( )

Incidence

per million

( )

FIGURE 151-1 Incidence of listeriosis and percentage of ready-to-eat meat and poultry products with cultures that yielded L. monocytogenes, United States, 1989–2019.

Incidence data are from the Center for Disease Control and Prevention’s active sentinel site surveillance and include data from an early surveillance system (1986–1995)

and from the Foodborne Diseases Active Surveillance Network (FoodNet) database (1996–2019). The incidence was 7.3 cases per million in 1986. Product data for 1990–2017

are publicly available through the U. S. Department of Agriculture Food Safety and Inspection Service Microbiological Testing Program for Ready-to-Eat Meat and Poultry

Products.

1210 PART 5 Infectious Diseases

diagnosis of listeriosis in a hospitalized patient with new symptoms

should prompt investigation into the food provided during hospitalization as a source. In fact, outbreaks have been traced to food served

to hospitalized patients, especially those with immunocompromising

conditions; implicated foods include sandwiches, butter, precut celery,

Camembert cheese, sausage, tuna salad, and ice cream. A large 2017–

2018 outbreak of listeriosis in South Africa, linked to a ready-to-eat

processed meat product, disproportionately affected people living with

HIV and pregnant women. No outbreak-associated cases were detected

in the 15 other countries that imported the product; this discrepancy

suggests that listeriosis is underrecognized in low- to middle-income

countries, particularly those with a high prevalence of HIV infection.

■ CLINICAL MANIFESTATIONS

L. monocytogenes infection can manifest in several ways. The incubation period differs according to host factors and dose consumed:

on average, this interval is <24 h for gastroenteritis and ~11 days for

invasive disease, although it can be much longer. Data from outbreak

investigations suggest that the incubation period is longer in pregnant

women than in nonpregnant adults.

Febrile Gastroenteritis Listeria organisms typically pass through

healthy people without causing symptoms, but acute febrile gastroenteritis can occur. Outbreak investigations of L. monocytogenes febrile

gastroenteritis have identified high organism density in implicated

foods, suggesting that a large inoculum must be ingested to cause illness. Major manifestations are fever, diarrhea, headache, and constitutional symptoms. Illness is usually self-limited, with symptoms lasting

an average of 1–3 days.

Bacteremia Bacteremia without a focus is the most common manifestation of invasive listeriosis. Major features are fever, chills, myalgias,

and arthralgias, sometimes preceded by nausea or diarrhea—markers

of the initial gut infection. Bacteremia can cause neurolisteriosis or

localized infection at other sites, in which case the diagnosis may be

suggested by neurologic or other focal findings. In a large French

cohort study, the 3-month mortality rate for L. monocytogenes bacteremia was 46%; death was associated with older age, female sex, neoplasia, multiorgan failure, worsening of preexisting organ dysfunction,

and monocytopenia (<200 cells/μL).

Neurolisteriosis L. monocytogenes has an affinity for the central nervous system. Neurolisteriosis is the second most common

manifestation of invasive listeriosis. Signs of meningitis along with

altered mental status, seizures, or focal neurologic findings suggest

meningoencephalitis. A recent French cohort study found that 84%

of patients with neurolisteriosis presented with meningoencephalitis.

Isolate-based surveillance systems may not distinguish between meningitis and meningoencephalitis.

Onset of neurologic disease can be sudden or subacute, taking place

over the course of several days. Patients typically have fever, headache,

nausea, and vomiting—findings similar to those in other bacterial

meningitides—but nuchal rigidity and meningeal signs occur less

commonly than in the latter conditions. Most patients (~75%) have

cerebrospinal fluid (CSF) white blood cell counts of <1000/μL (range,

100–5000/μL). CSF neutrophil predominance is typically less pronounced than in other bacterial meningitides. Approximately 30–40%

of patients have low CSF glucose levels. Gram’s staining of CSF sediment can show the expected gram-positive rods but commonly shows

no organisms and sometimes shows gram-positive cocci, diplococci, or

diphtheroids. In a U.S. study, L. monocytogenes caused <5% of cases of

community-acquired bacterial meningitis in adults.

Uncommon neurolisteriosis manifestations include cerebritis, focal

abscess, and rhombencephalitis (encephalitis of the cerebellum and

brainstem). Patients with macroscopic abscesses often have positive

blood cultures, but CSF findings may be normal in the absence of

concurrent meningitis. Abscesses may be misdiagnosed as a primary

or metastatic malignancy; they rarely occur in the cerebellum or spinal

cord. Rhombencephalitis disproportionately affects otherwise healthy

older adults. The classic presentation is biphasic, beginning with fever

and headache and continuing after several days with signs of brainstem

or cerebellar involvement, such as asymmetric cranial nerve palsies,

ataxia, tremor, hemiparesis, or hemisensory deficits. Nearly half of

patients with rhombencephalitis experience respiratory failure. The

diagnosis may be delayed by the subacute course and by CSF findings,

which are often only minimally abnormal. MRI is superior to CT for

the diagnosis of neurolisteriosis, including rhombencephalitis.

Overall, the 3-month mortality rate for neurolisteriosis was 30% in

a recent French cohort study; death was associated with the same risk

factors as those documented for bacteremia. Neurolisteriosis-associated

mortality was also higher among patients with a positive blood culture

and among those treated with dexamethasone. Nearly half of survivors

had long-term neurologic impairment.

Focal infections Hematogenous dissemination of L. monocytogenes infrequently causes endocarditis, pneumonia, localized abscesses

in the liver or other internal organs, peritonitis, septic arthritis, osteomyelitis, urinary tract infection, or skin lesions. Direct inoculation has

been reported as a rare cause of ocular infection, skin infection, and

lymphadenitis.

Infection in Pregnant Women and Neonates Pregnancyassociated listeriosis is most common in the third trimester, presumably because of impaired maternal cell-mediated immunity. Typically,

pregnant women either are asymptomatic or have a mild, flulike illness

with fever, headache, myalgias, or arthralgias. Neurolisteriosis and

death are rare in pregnant women without other risk factors. Although

nearly all infected women fully recover, only a minority (~5%) have a

normal delivery and postpartum course. In a study of 107 pregnancies

in which L. monocytogenes was isolated from the mother, fetus, or

neonate, 24% ended with fetal loss, 45% with premature birth, and

21% with abnormal delivery at term (i.e., fever, meconium release into

amniotic fluid, abnormal fetal heart rate). Moreover, 88% of the 82

live-born neonates were ill, including 49% who required intensive care.

Fetal loss is uncommon after 29 weeks of gestation. Granulomatosis

infantiseptica is a severe in utero infection caused by L. monocytogenes

and characterized by disseminated microabscesses and granulomas in

the skin, liver, and spleen; most infants with this condition are stillborn

or die soon after birth. Neonatal infection usually manifests in one of

two ways: early-onset sepsis is hypothesized to result from in utero

infection because it is typically diagnosed within 48 h after birth and

is often associated with prematurity, whereas late-onset meningitis is

thought to result from infection acquired at or soon after birth because

it is typically diagnosed at ~2 weeks of age in full-term infants. A study

of 128 pregnancy-associated listeriosis cases found that 47 (62%) of 76

ill neonates had early-onset disease. The case–fatality rate for neonatal

listeriosis is 10–50%.

■ DIAGNOSIS

Because symptoms of listeriosis overlap with those of other infections,

a high index of suspicion can facilitate timely diagnosis. Pregnant

women with suspected listeriosis should have blood drawn for cultures,

although blood cultures are positive only about half the time. Isolation

of L. monocytogenes from a normally sterile site, such as blood, CSF,

amniotic fluid, placental tissue, or fetal tissue, is diagnostic. Listeria

must be distinguished from other gram-positive rods, especially diphtheroids. L. monocytogenes can be isolated from sterile specimens on

routine medium; selective enrichment medium (such as PALCAM

Listeria Selective Agar or Oxford Agar) enhances the capacity for

isolation of the organism from nonsterile specimens, such as stool.

Stool culture is not indicated in the evaluation of invasive listeriosis;

culture on selective medium can be helpful for outbreak investigations

of febrile gastroenteritis. Commercially available multiplex polymerase

chain reaction panels for CSF specimens include L. monocytogenes as

a target and may be a useful adjunct to culture. Matrix-assisted laser

desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry can rapidly identify an isolate as L. monocytogenes. Whole-genome

sequencing has been a valuable tool for solving outbreaks of listeriosis,

including a nosocomial outbreak associated with ice cream served in

hospital milkshakes.

1211CHAPTER 152 Tetanus

TREATMENT

Infections Caused by Listeria monocytogenes

L. monocytogenes treatment has not been evaluated in clinical trials.

Recommendations are based on in vitro animal studies and observational clinical data. High-dose ampicillin (adult dose, 2 g IV every 4 h)

or penicillin G (adult dose, 4 million units IV every 4 h) constitutes

first-line therapy. Because penicillins are only weakly bactericidal

against L. monocytogenes, many experts recommend adding gentamicin for synergy (1.0–1.7 mg/kg every 8 h if renal function is normal),

particularly if the infection is severe. Small studies have had varying

results with regard to the benefits of gentamicin. A large study provided evidence favoring amoxicillin–gentamicin as first-line therapy.

Patients who are allergic to penicillin should undergo desensitization or be treated with trimethoprim-sulfamethoxazole (TMP-SMX;

5 mg/kg per dose of the trimethoprim component, given IV every

6–12 h). TMP-SMX should be avoided during the first trimester

because it has been associated with neural tube and cardiovascular

defects and in the perinatal period because it may increase the risk of

kernicterus. Resistance to TMP-SMX has been reported; thus antibiotic susceptibility testing should be performed if this drug is considered. Treatment failures have been reported with meropenem despite

in vitro susceptibility of the organism. L. monocytogenes is susceptible

in vitro to several other drugs, including vancomycin, linezolid, tetracycline, macrolides, and fourth-generation fluoroquinolones (e.g.,

moxifloxacin), but relevant clinical reports are limited. Cephalosporins are not effective. A retrospective study of 31 patients found

significantly reduced survival rates among patients treated with

dexamethasone; the authors suggest avoiding this drug in neurolisteriosis. Prepartum antibiotic treatment of pregnant women with

listeriosis enhances the chance of delivering a healthy infant.

The optimal duration of antibiotic therapy has not been established. Treatment duration usually depends on the clinical syndrome, disease severity, patient attributes, and response to treatment.

The typical minimal treatment duration is 2 weeks for bacteremia,

2 weeks for early-onset neonatal disease, 3 weeks for meningitis,

4–6 weeks for endocarditis, and 6–8 weeks for brain abscess or

encephalitis. Longer courses may be needed when patients are

immunocompromised or are not improving as expected. Patients

with neurolisteriosis do not routinely require a follow-up lumbar

puncture if they are improving clinically during antibiotic therapy.

■ PREVENTION

Care of patients with listeriosis should be undertaken with standard

precautions because person-to-person transmission is rare. Implementation of general precautions to prevent foodborne illness can help

prevent listeriosis. These measures include fully cooking meats; washing fresh produce; cleaning hands, utensils, and kitchen surfaces after

handling uncooked foods; and avoiding unpasteurized dairy products.

Persons at increased risk for listeriosis should take additional precautions, including avoiding soft cheeses (particularly those made with

unpasteurized milk) and either avoiding ready-to-eat and delicatessen

foods (including meats, hot dogs, and smoked seafood) or heating these

foods until the internal temperature is 165°F or until they are steaming

hot. Additional CDC recommendations can be found at www.cdc.gov/

listeria/prevention.html. Hospital dietary services should implement

safe food-preparation procedures for immunocompromised patients

and should not serve these patients higher-risk foods. Testing and

treatment are not indicated for an asymptomatic person who has eaten

a product recalled because of L. monocytogenes contamination, even if

the person has risk factors for invasive listeriosis. TMP-SMX given as

prophylaxis for Pneumocystis jirovecii infection (e.g., to persons infected

with HIV or organ transplant recipients) helps prevent listeriosis.

■ FURTHER READING

Charlier C et al: Clinical features and prognostic factors of listeriosis:

The MONALISA National Prospective Cohort Study. Lancet Infect

Dis 17:510, 2017.

Farley MM: Listeria monocytogenes, in Principles and Practice of

Pediatric Infectious Diseases, 5th ed, Long SS et al (eds). Philadelphia,

Elselvier, 2018, pp 781–785.

Gottlieb SL et al: Multistate outbreak of listeriosis linked to turkey

deli meat and subsequent changes in US regulatory policy. Clin Infect

Dis 42:29, 2006.

Hof H: An update on the medical management of listeriosis. Expert

Opin Pharmacother 5:1727, 2004.

Mccollum JT et al: Multistate outbreak of listeriosis associated with

cantaloupe. N Engl J Med 369:944, 2013.

Radoshevich L, Cossart P: Listeria monocytogenes: Towards a complete picture of its physiology and pathogenesis. Nat Rev Microbiol

16:32, 2018.

Silk BJ et al: Foodborne listeriosis acquired in hospitals. Clin Infect

Dis 59:532, 2014.

Thomas J et al: Outbreak of listeriosis in South Africa associated with

processed meat. N Engl J Med 382:632, 2020.

Tetanus is an acute disease manifested by skeletal muscle spasm and

autonomic nervous system disturbance. It is caused by a powerful

neurotoxin produced by the bacterium Clostridium tetani and is completely preventable by vaccination. C. tetani is found throughout the

world, and tetanus commonly occurs where the vaccination coverage

rate is low. In developed countries, the disease is seen occasionally in

individuals who are incompletely vaccinated. In any setting, established

tetanus is a severe disease with a high mortality rate.

■ DEFINITION

Tetanus is diagnosed on clinical grounds (sometimes with supportive

laboratory confirmation of the presence of C. tetani; see “Diagnosis,”

below), and case definitions are often used to facilitate clinical and

epidemiologic assessments. The Centers for Disease Control and

Prevention (CDC) defines probable tetanus as “an acute illness with

muscle spasms or hypertonia in the absence of a more likely diagnosis.”

Neonatal tetanus is defined by the World Health Organization (WHO)

as “an illness occurring in a child who has the normal ability to suck

and cry in the first 2 days of life but who loses this ability between days

3 and 28 of life and becomes rigid and has spasms.” Given the unique

presentation of neonatal tetanus, the history generally permits accurate

classification of the illness with a high degree of probability. Maternal

tetanus is defined by the WHO as tetanus occurring during pregnancy

or within 6 weeks after the conclusion of pregnancy (whether with

birth, miscarriage, or abortion).

■ ETIOLOGY

C. tetani is an anaerobic, gram-positive, spore-forming rod whose

spores are highly resilient and can survive readily in the environment

throughout the world. Spores resist boiling and many disinfectants. In

addition, C. tetani spores and bacilli survive in the intestinal systems

of many animals, and fecal carriage is common. The spores or bacteria

enter the body through abrasions, wounds, or (in the case of neonates)

the umbilical stump. Once in a suitable anaerobic environment, the

organisms grow, multiply, and release tetanus toxin, an exotoxin that

enters the nervous system and causes disease. Very low concentrations

of this highly potent toxin can result in tetanus (minimal lethal human

dose, 2.5 ng/kg).

In 20–30% of cases of tetanus, no puncture entry wound is found.

Superficial abrasions to the limbs are the most common infection

sites in adults. Deeper infections (e.g., attributable to open fracture,

152 Tetanus

C. Louise Thwaites, Lam Minh Yen