Listeriosis

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For further information, see CMDT Part 33-08: Listeriosis

Key Features

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Essentials of Diagnosis

Ingestion of contaminated food product
Undifferentiated fever in a pregnant woman in her third trimester
Altered mental status and fever in an elderly or immunocompromised patient
Obtain blood and cerebral spinal fluid cultures to confirm diagnosis

General Considerations

Listeria monocytogenes is a facultative, motile, gram-positive rod that is capable of invading several cell types and causes intracellular infection
Most cases of infection are sporadic, but outbreaks have been traced to eating contaminated food, including
- Unpasteurized dairy products
- Hot dogs
- Delicatessen meats
- Cantaloupes
- Ricotta cheese
Outbreaks have been associated with significant morbidity and mortality in infected persons

Clinical Findings

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Five types of infection are recognized
Infection during pregnancy
- Usually in the last trimester
- Produces a mild febrile illness without an apparent primary focus and may resolve without therapy
- However, approximately 1 in 5 pregnancies complicated by listeriosis result in spontaneous abortion or stillbirth and surviving infants are at risk for clinical neonatal listeriosis
Granulomatosis infantisepticum
- Neonatal infection
- Characterized by disseminated abscesses and granulomas and a high mortality rate
Bacteremia with or without sepsis syndrome
- An infection of neonates or immunocompromised adults
- Presentation is a febrile illness without a recognized source
Meningitis
- Affects infants younger than 2 mo and adults, ranking third among the common causes of bacterial meningitis
- Adults with meningitis are usually immunocompromised
- Cases have been associated with HIV infection
Focal infections occur rarely and include
- Adenitis
- Brain abscess
- Endocarditis
- Osteomyelitis
- Arthritis

Diagnosis

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Positive blood or cerebrospinal fluid culture
In meningitis, cerebrospinal fluid shows a neutrophilic pleocytosis

Treatment

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Tables 30–4 and 30–2
Drug of choice is ampicillin, 8–12 g/day intravenously in four to six divided doses (the higher dose is recommended in cases of meningitis) for 14–21 days
Gentamicin at 5 mg/kg/day once or in divided doses intravenously is synergistic with ampicillin; combination therapy may be considered during the first few days of treatment to enhance eradication of organisms
Trimethoprim-sulfamethoxazole
- An effective alternative for patients who are allergic to penicillin
- The dose of trimethoprim component is 10–15 mg/kg/day

Table 30–2.Initial antimicrobial therapy for purulent meningitis of unknown cause.

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Table 30–2. Initial antimicrobial therapy for purulent meningitis of unknown cause.

Population

Usual Microorganisms

Standard Therapy

18–50 years

Streptococcus pneumoniae, Neisseria meningitidis

Vancomycin¹ plus ceftriaxone²

Over 50 years

S pneumoniae, N meningitidis, Listeria monocytogenes, gram-negative bacilli, group B streptococcus

Vancomycin¹ plus ampicillin,³ plus ceftriaxone²

Impaired cellular immunity

L monocytogenes, gram-negative bacilli, S pneumoniae

Vancomycin¹ plus ampicillin³ plus cefepime⁴

Postsurgical or posttraumatic

Staphylococcus aureus, S pneumoniae, aerobic gram-negative bacilli, coagulase-negative staphylococci,⁵ diphtheroids (eg, Propionibacterium acnes)⁵ (uncommon)

Vancomycin¹ plus cefepime⁴

¹Given to cover highly penicillin- or cephalosporin-resistant pneumococci. The dose of vancomycin is 15 mg/kg/dose intravenously every 8 hours. Vancomycin trough levels should be maintained at > 15 mcg/mL. Stopped if the causative organism is susceptible to ceftriaxone.

²Ceftriaxone can often be used safely in most patients with a history of penicillin allergy (aztreonam can be considered for empiric coverage of gram-negative bacilli in patients with Type 1 IgE-mediated penicillin and cephalosporin allergy). The usual dose of ceftriaxone is 2 g intravenously every 12 hours. If the organism is susceptible to penicillin, 3–4 million units intravenously every 4 hours is given.

³In severely ill patients, ampicillin is used when L monocytogenes infection is a consideration. For confirmed infection due to L monocytogenes, gentamicin is sometimes added to ampicillin. (For patients with Type 1 IgE-mediated penicillin allergy, trimethoprim-sulfamethoxazole [TMP-SMZ] in a dosage of 15–20 mg/kg/day of TMP in 3 or 4 divided doses can be considered.) The dose of ampicillin is usually 2 g intravenously every 4 hours.

⁴Cefepime is given in a dose of 3 g intravenously every 8 hours.

⁵Primarily associated with presence of hardware.

Table 30–4.Medication of choice for suspected or documented microbial pathogens (listed in alphabetical order, within classes).

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Table 30–4. Medication of choice for suspected or documented microbial pathogens (listed in alphabetical order, within classes).

Suspected or Proved Etiologic Agent

Medication(s) of First Choice

Alternative Medication(s)

Gram-negative Cocci

Moraxella catarrhalis

Cefuroxime, amoxicillin-clavulanic acid

Ceftriaxone, cefuroxime axetil, a fluoroquinolone,¹ a macrolide,² a tetracycline,³ TMP-SMZ⁴

Neisseria gonorrhoeae (gonococcus)

Ceftriaxone + azithromycin or doxycycline

Cefixime + azithromycin or doxycycline⁵

Neisseria meningitidis (meningococcus)

Penicillin⁶

Ceftriaxone, ampicillin

Gram-positive Cocci

Enterococcus faecalis

Ampicillin ± gentamicin⁷

Vancomycin ± gentamicin

Enterococcus faecium

Vancomycin ± gentamicin⁷

Linezolid,⁸ quinupristin-dalfopristin,⁸ daptomycin,⁸ tigecycline,⁸ tedizolid,⁸ oritavancin⁸

Streptococcus, hemolytic, groups A, B, C, G

Penicillin⁶

Macrolide,² a cephalosporin,⁹ vancomycin, clindamycin

Staphylococcus, methicillin-resistant

Vancomycin

TMP-SMZ,⁴ doxycycline, minocycline, linezolid,⁸ tedizolid,⁸ daptomycin,⁸ televancin,⁸ dalbavancin,⁸ oritavancin,⁸ ceftaroline, delafloxacin

Staphylococcus, methicillin-susceptible

Penicillinase-resistant penicillin¹⁰

Vancomycin, a cephalosporin,⁹ clindamycin, amoxicillin-clavulanic acid, ampicillin-sulbactam

Streptococcus pneumoniae¹¹ (pneumococcus)

Penicillin⁶

A cephalosporin,⁹ vancomycin, clindamycin, a tetracycline,³ respiratory fluoroquinolones¹

Viridans streptococci

Penicillin⁶

Cephalosporin,⁹ vancomycin

Gram-negative Rods

Acinetobacter

Imipenem, meropenem

Tigecycline, minocycline, doxycycline, aminoglycosides,¹² colistin, cefiderocol

Bacteroides, gastrointestinal strains

Metronidazole

Ampicillin-sulbactam, piperacillin-tazobactam, ertapenem

Brucella

Doxycycline + rifampin³

TMP-SMZ⁴ ± gentamicin; ciprofloxacin + rifampin

Burkholderia mallei (glanders)

Streptomycin + tetracycline³

Chloramphenicol + streptomycin

Burkholderia pseudomallei (melioidosis)

Ceftazidime

Tetracycline,³ TMP-SMZ,⁴ amoxicillin-clavulanic acid, imipenem or meropenem

Campylobacter jejuni

Azithromycin

A fluoroquinolone¹

Enterobacter

Ertapenem, imipenem, meropenem, cefepime

Aminoglycoside, a fluoroquinolone,¹ TMP-SMZ⁴

Escherichia coli (uncomplicated outpatient urinary infection)

Nitrofurantoin, fosfomycin

Fluoroquinolones,¹ TMP-SMZ,⁴ oral cephalosporin

Escherichia coli (sepsis)¹³

Cefotaxime, ceftriaxone

Ertapenem,¹³ imipenem¹³ or meropenem,¹³ aminoglycosides,¹² aztreonam, ticarcillin-clavulanate, piperacillin-tazobactam, ceftazidime-avibactam,^13,15 ceftolozane-tazobactam,^13,14 meropenem/vaborbactam,¹⁵ imipenem/cilastatin-relebactam^13,14,15

Haemophilus (respiratory infections, otitis)

Ampicillin-clavulanate

Doxycycline, azithromycin, ceftriaxone, cefuroxime, cefuroxime axetil, TMP-SMZ⁴

Haemophilus (serious infection)

Ceftriaxone

Aztreonam

Helicobacter pylori

Proton pump inhibitor (PPI), clarithromycin, amoxicillin, and metronidazole

PPI, clarithromycin, and amoxicillin or metronidazole

Klebsiella¹³

Ceftriaxone

TMP-SMZ,⁴ aminoglycoside,¹² ertapenem,¹³ imipenem¹³ or meropenem,¹³ a fluoroquinolone,¹ aztreonam, ticarcillin-clavulanate, piperacillin-tazobactam, ceftazidime-avibactam,¹³ ceftolozane-tazobactam,^13,14 meropenem/vaborbactam,¹⁵ imipenem/cilastatin-relebactam^13,14,15

Legionella species (pneumonia)

Azithromycin, or fluoroquinolones¹ ± rifampin

Doxycycline ± rifampin

Prevotella, oropharyngeal strains

Clindamycin

Metronidazole

Proteus mirabilis

Ampicillin

TMP-SMZ,⁴ a fluoroquinolone,¹ a cephalosporin⁹

Proteus vulgaris and other species (Morganella, Providencia)

Ceftriaxone

Ertapenem, imipenem or meropenem, TMP-SMZ,⁴ a fluoroquinolone¹

Pseudomonas aeruginosa

Piperacillin-tazobactam or ceftazidime or cefepime, or imipenem or meropenem or doripenem or aztreonam ± aminoglycoside¹²

Ciprofloxacin (or levofloxacin) ± piperacillin-tazobactam; ciprofloxacin (or levofloxacin) ± ceftazidime; ciprofloxacin (or levofloxacin) ± cefepime; ceftazidime-avibactam¹³; ceftolozane-tazobactam,¹³ cefiderocol, imipenem/cilastatin-relebactam

Salmonella (bacteremia)

Ceftriaxone

A fluoroquinolone¹

Serratia

Carbapenem

TMP-SMZ,⁴ a fluoroquinolone,¹ ceftriaxone

Shigella

Azithromycin, ciprofloxacin, or ceftriaxone

TMP-SMZ⁴

Vibrio (cholera, sepsis)

A tetracycline³

TMP-SMZ,⁴ a fluoroquinolone¹

Yersinia pestis (plague)

Streptomycin ± a tetracycline³

Chloramphenicol, TMP-SMZ⁵

Gram-positive Rods

Actinomyces

Penicillin⁶

Tetracycline,³ clindamycin

Bacillus (including anthrax)

Penicillin⁶

A macrolide,² a fluoroquinolone¹

Clostridium (eg, gas gangrene, tetanus)

Penicillin⁶

Metronidazole, clindamycin, imipenem, or meropenem

Corynebacterium diphtheria

Macrolide²

Penicillin⁶

Corynebacterium jeikeium

Vancomycin

Linezolid

Listeria

Ampicillin ± aminoglycoside¹²

TMP-SMZ⁴

Acid-fast Rods

Mycobacterium avium complex

Clarithromycin or azithromycin + ethambutol, ± rifabutin

Amikacin, ciprofloxacin

Mycobacterium fortuitum-chelonei

Cefoxitin + clarithromycin

Amikacin, rifampin, sulfonamide, doxycycline, linezolid

Mycobacterium kansasii

INH + rifampin ± ethambutol

Clarithromycin, azithromycin, ethionamide, cycloserine

Mycobacterium leprae

Dapsone + rifampin ± clofazimine

Minocycline, ofloxacin, clarithromycin

Mycobacterium tuberculosis¹⁶

Isoniazid (INH) + rifampin + pyrazinamide ± ethambutol

Other antituberculous drugs (see Tables 9–14 and 9–15)

Nocardia

TMP-SMZ⁴

Minocycline, imipenem or meropenem, linezolid

Spirochetes

Borrelia burgdorferi (Lyme disease)

Doxycycline, amoxicillin, cefuroxime axetil

Ceftriaxone, penicillin, azithromycin

Borrelia recurrentis (relapsing fever)

Doxycycline³

Penicillin⁶

Leptospira

Penicillin⁶

Doxycycline,³ ceftriaxone

Treponema pallidum (syphilis)

Penicillin⁶

Doxycycline, ceftriaxone

Treponema pertenue (yaws)

Penicillin⁶

Doxycycline

Mycoplasmas

Azithromycin or doxycycline

A fluoroquinolone¹

Chlamydiae

C pneumoniae

Doxycycline³

Azithromycin, a fluoroquinolone^1,17

C psittaci

Doxycycline

Chloramphenicol

C trachomatis (urethritis or pelvic inflammatory disease)

Doxycycline or azithromycin

Levofloxacin, ofloxacin

Rickettsiae

Doxycycline³

Chloramphenicol, a fluoroquinolone¹

¹Fluoroquinolones include ciprofloxacin, levofloxacin, moxifloxacin, and others. Gemifloxacin, levofloxacin, and moxifloxacin, the so-called respiratory fluoroquinolones, demonstrate the most reliable activity against penicillin-resistant S pneumoniae and other respiratory infection pathogens. Delafloxacin is predictably active against methicillin-resistant S aureus (MRSA).

²Azithromycin is the preferred macrolide due to increased safety profile and minimal drug interaction potential.

³All tetracyclines have similar activity against most microorganisms. Minocycline (the most active tetracycline) and doxycycline are more active than tetracycline against S aureus.

⁴TMP-SMZ is a mixture of 1 part trimethoprim and 5 parts sulfamethoxazole.

⁵Test of cure required if ceftriaxone not used.

⁶Penicillin G is preferred for parenteral injection; penicillin V for oral administration.

⁷Addition of gentamicin indicated only for severe enterococcal infections (eg, endocarditis, meningitis).

⁸Linezolid, tedizolid, daptomycin, televancin, dalbavancin, and oritavancin should be reserved for the treatment of vancomycin-resistant isolates or in patients intolerant of vancomycin.

⁹Most intravenous cephalosporins (with the exception of ceftazidime) are active against streptococci and staphylococci.

¹⁰Parenteral nafcillin or oxacillin; oral dicloxacillin, cloxacillin, or oxacillin.

¹¹Infections caused by isolates with intermediate resistance may respond to high dose penicillin or ceftriaxone or the respiratory fluoroquinolones (gemifloxacin, levofloxacin, and moxifloxacin). Infections caused by highly penicillin-resistant isolates should be treated with vancomycin. Penicillin-resistant pneumococci are often resistant to macrolides, tetracyclines, and TMP-SMZ.

¹²Aminoglycosides—gentamicin, tobramycin, amikacin, netilmicin—should be chosen on the basis of local patterns of susceptibility.

¹³Extended beta-lactamase–producing (ESBL) isolates should be treated with a carbapenem. If a carbapenem cannot be used, ceftazidime-avibactam or possibly ceftolozane-tazobactam can be considered.

¹⁴Ceftolozane-tazobactam, cefiderocol, imipenem/cilastatin-relebactam and occasionally ceftazidime-avibactam may be active against multidrug-resistant P aeruginosa.

¹⁵Consider in cases of infection due to carbapenemase-producing Enterobacteriaceae.

¹⁶Resistance is common and susceptibility testing must be performed.

¹⁷Ciprofloxacin has inferior antichlamydial activity compared with levofloxacin or ofloxacin.

±, alone or combined with.

Table 9–14.Characteristics of antituberculous medications.

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Table 9–14. Characteristics of antituberculous medications.

Medication

Most Common Side Effects

Tests for Side Effects

Drug Interactions

Remarks

Isoniazid

Peripheral neuropathy, hepatitis, rash, mild CNS effects.

AST and ALT; neurologic examination.

Phenytoin (synergistic); disulfiram.

Bactericidal to both extracellular and intracellular organisms. Pyridoxine, 25–50 mg orally daily is given as prophylaxis for neuritis; 50–100 mg orally daily as treatment for it.

Rifampin

Hepatitis, fever, rash, flu-like illness, gastrointestinal upset, bleeding problems, kidney failure.

CBC, platelets, AST and ALT.

Rifampin inhibits the effect of oral contraceptives, quinidine, corticosteroids, warfarin, methadone, digoxin, oral hypoglycemics; aminosalicylic acid may interfere with absorption of rifampin. Significant interactions with protease inhibitors and nonnucleoside reverse transcriptase inhibitors.

Bactericidal to all populations of organisms. Colors urine and other body secretions orange. May discolor contact lenses.

Rifapentine

Bone marrow suppression, hematuria/pyuria, hepatitis, gastrointestinal upset, flu-like illness.

CBC, platelets, AST and ALT.

Strong cytochrome P450 inducer with multiple drug interactions. Use in HIV patients receiving antiretroviral therapy should be limited to experts in antiretroviral therapy.

Bactericidal to both extracellular and intracellular organisms. Colors urine and other body secretions orange. Long half-life, can be administered weekly in LTBI prophylaxis. Not for use in induction phase of therapy.

Pyrazinamide

Hyperuricemia, hepatotoxicity, rash, gastrointestinal upset, joint aches.

Uric acid, AST, ALT.

Rare.

Bactericidal to intracellular organisms.

Ethambutol

Optic neuritis (reversible with discontinuance of drug; rare at 15 mg/kg); rash.

Red-green color discrimination and visual acuity.

Rare.

Bacteriostatic to both intracellular and extracellular organisms. Mainly used to inhibit development of resistant mutants. Use with caution in kidney disease or when ophthalmologic testing is not feasible.

Streptomycin

Eighth nerve damage, nephrotoxicity.

Vestibular function (audiograms); BUN and creatinine.

Neuromuscular blocking agents may be potentiated and cause prolonged paralysis.

Bactericidal to extracellular organisms. Use with caution in older patients or those with kidney disease.

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CBC, complete blood count; LTBI, latent tuberculosis infection.

Table 9–15.Recommended dosages for the initial treatment of tuberculosis.¹

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Table 9–15. Recommended dosages for the initial treatment of tuberculosis.¹

Medication

Daily²

Cost³/Day

Twice a Week²

Cost³/Wk

Three Times a Week²

Cost³/Wk

Isoniazid

5 mg/kg

Max: 300 mg/dose

$0.31/300 mg

15 mg/kg

Max: 900 mg/dose

$1.86

15 mg/kg

Max: 900 mg/dose

$2.79

Rifampin

10 mg/kg

Max: 600 mg/dose

$2.66/600 mg

10 mg/kg

Max: 600 mg/dose

$5.32

10 mg/kg

Max: 600 mg/dose

$7.98

Pyrazinamide

18.2–26.3 mg/kg

Max: 2 g/dose

$13.95/2 g

Weight-based dosing: see references below¹

—

Weight-based dosing: see references below¹

—

Ethambutol

14.5–21.1 mg/kg

Max: 1.6 g/dose

$3.74/1.6 g

Weight-based dosing: see references below¹

—

Weight-based dosing: see references below¹

—

¹Data from Nahid P et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016 Oct 1;63(7):e147–95.

²All dosing regimens should be used with directly observed therapy.

³Average wholesale price (AWP, for AB-rated generic when available) for quantity listed. Source: IBM Micromedex. Red Book (electronic version). IBM Watson Health, Greenwood Village, CO, USA. Available at https://www.micromedexsolutions.com/ (cited March 25, 2020). AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions.

Also available at www.cdc.gov/tb/topic/treatment/guidelinehighlights.htm.

Outcome

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Prevention

At-risk patients (eg, pregnant women) should avoid unpasteurized milk products
Smoked seafoods, cold cuts, hot dogs, and meat spreads also carry risk
Thoroughly cook animal source food and wash raw vegetables

References

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Jackson BR et al; Centers for Disease Control and Prevention (CDC). Notes from the field: listeriosis associated with stone fruit—United States, 2014. MMWR Morb Mortal Wkly Rep. 2015 Mar 20;64(10):282–3.
[PubMed: 25789745]

Madjunkov M et al. Listeriosis during pregnancy. Arch Gynecol Obstet. 2017 Aug;296(2):143–52.
[PubMed: 28536811]

Salama PJ et al. Learning from listeria: safer food for all. Lancet. 2018 Jun 9;391(10137):2305–6.
[PubMed: 29900862]

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Key Features

Essentials of Diagnosis

General Considerations

Clinical Findings

Diagnosis

Treatment

Outcome

Prevention

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