Gram Positives

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1. Name two Enterococcus species inherently resistant to vancomycin.

Answer below.

E gallinarum and E casseliflavus/E flavescens demonstrate intrinsic low-level resistance to vancomycin. Acquired vancomycin resistance can be seen in certain E faecium and E faecalis strains, as well as E raffinosus, E avium, and E durans.

American Academy of Pediatrics. Non-Group A or B Streptococcal and Enterococcal Infections.. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics. 2021: 713-717

2. Which Streptococcus species groups are included among viridans Streptococci? Name 5.

Answer below.

S mutans group, S anginosus group, S mitis group, S sanguinis group, S salivarius group.

3. Which species are included in the S anginosus group?

Answer below.

S anginosus, S constellatus, S intermedius.

4. Which genera are included in what are often called nutritionally-variant streptococci?

Answer below.

Abiotrophia and Granulicatella.

5. What are the cutoffs (in terms of minimum inhibitory concentration) for relatively resistant and resistant strains of viridans Streptococci when it comes to penicillin in endocarditis?

Answer below.

Susceptible: MIC ≤0.12 ug/mL

Relatively resistant: >0.12 ug/mL and <0.5 ug/mL

Resistant: ≥0.5 ug/mL

6. What proportion of Group B Streptococcus can be clindamycin resistant in the United States?

Answer below.

20% and greater

Prevention of group B streptococcal early-onset disease in newborns. ACOG Committee Opinion No. 797. American College of Obstetricians and Gynecologists. Obstet Gynecol 2020;135:e51–72.

7. Name the 5 major Jones criteria for diagnosis of rheumatic fever.

Answer below.

Carditis, arthritis (can be monoarthritis in high-risk populations, otherwise only polyarthritis counts in low-risk populations), chorea, erythema marginatum, subcutaneous nodules.

Gewitz MH, Baltimore RS, Tani LY, Sable CA, Shulman ST, Carapetis J, et al. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association. Circulation. 2015 May 19;131(20):1806-18.

8. Name the minor Jones criteria for diagnosis of rheumatic fever.

Answer below.

Fever (≥38.5 C), arthralgia (can be monoarthralgia in high-risk populations, otherwise only polyarthralgia counts in low-risk populations), elevated acute phase reactants (CRP ≥3.0 mg/dL, ESR ≥30 mm/hr in high risk populations, otherwise only ≥60 mm/hr counts in low risk populations), and prolonged PR interval.

9. How long should a patient with acute rheumatic fever WITHOUT carditis receive secondary prophylaxis (according to AHA guidelines)?

Answer below.

Until the age of 21, or 5 years after the last episode of acute rheumatic fever, whichever is longer.

Kumar RK, Antunes MJ, Beaton A, Mirabel M, Nkomo VT, Okello E, et al. Contemporary Diagnosis and Management of Rheumatic Heart Disease: Implications for Closing the Gap: A Scientific Statement From the American Heart Association. Circulation. 2020 Nov 17;142(20):e337-e357.

10. How long should a patient with acute rheumatic fever WITH carditis WITHOUT residual disease receive secondary prophylaxis (according to AHA guidelines)?

Answer below.

Until the age of 21, or 10 years after the last episode of acute rheumatic fever, whichever is longer.

11. How long should a patient with acute rheumatic fever WITH carditis WITH residual disease receive secondary prophylaxis (according to AHA guidelines)?

Answer below.

Until the age of 40, or 10 years after the last episode of acute rheumatic fever, whichever is longer; sometimes lifetime prophylaxis is needed.

12. Describe Nocardia in terms of its staining and microscopic morphology.

Answer below.

Gram-positive, intracellular, nonmotile, filamentous. Because its cell walls contain mycolic acid, it can be partially acid-fast.

American Academy of Pediatrics. Nocardiosis. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics. 2021: 546-548

13. Which body site/fluid do some experts recommend imaging/sampling in patients with pulmonary nocardiosis due to its propensity for spreading here?

Answer below.

"Some experts recommend cerebrospinal fluid examination and/or neuroimaging in patient with pulmonary disease, even with a nonfocal neurologic examination," given Nocardia's neurotropism.

14. What is the drug of choice for treating mild Nocardia infections?

Answer below.

TMP-SMX

15. What is the recommended drug regimen for serious Nocardia infections (e.g. pulmonary infection, disseminated disease, CNS involvement)?

Answer below.

Combination therapy with TMP-SMX, amikacin, and a carbapenem-cilastatin or linezolid until susceptibilities are available is recommended. Such patients should be treated for 6-12 months and for at least 3 months after apparent cure. Immunocompromised patients and those with HIV may require therapy for longer, and in some instances suppressive therapy for life may be considered.

16. How are Actinomyces and Nocardia often described on Gram stain? How can the two be distinguished by staining?

Answer below.

Both are Gram-positive, beaded, filamentous, branching rods/bacilli. Nocardia is partially acid-fast and is an obligate aerobe. Actinomyces is microaerophilic or facultative anaerobic.

American Academy of Pediatrics. Actinomycosis. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics. 2021: 187-188

17. How are Actinomyces and Nocardia often described on Gram stain? How can the two be distinguished by staining?

Answer below.

Both are Gram-positive, beaded, filamentous, branching rods/bacilli. Nocardia is partially acid-fast and is an obligate aerobe. Actinomyces is microaerophilic or facultative anaerobic.

18. Which organism is a co-pathogen frequently detected with Actinomyces infection and may help serve as a surrogate predictor of the presence of actinomycosis?

Answer below.

Aggregatibacter actinomycetemcomitans.

19. What is the antibiotic of choice for actinomycosis?

Answer below.

Initial therapy should include intravenous penicillin G or ampicillin for 4-6 weeks, followed by high-dose oral penicillin for 6-12 months depending on extend of disease. Amoxicillin and doxycycline are alternative antibiotic choices. Additional antibiotics with activity include ceftriaxone, piperacillin-tazobactam, clarithromycin, linezolid, imipenem, and meropenem.

20. Describe Actinomyces colony morphology and microscopic appearance.

Answer below.

A israellii forms "spider-like" microcolonies in 48 hours.

Actinomyces appears as beaded, branched, Gram-positive bacilli with yellow "sulfur granules", which are actually dense aggregates of bacterial filaments mixed with inflammatory debris.

21. What is the drug of choice for Erysipelothrix rhusiopathiae infections?

Answer below.

Penicillin. Most strains are highly susceptible to penicillin, cephalosporins, and clindamycin.

Reboli AC, Farrar WE. Erysipelothrix rhusiopathiae: an occupational pathogen. Clin Microbiol Rev. 1989 Oct;2(4):354-9.

22. What is Kocuria frequently confused with in phenotypic laboratory testing?

Answer below.

Micrococcus and coagulase-negative Staphylococcus.

Purty S, Saranathan R, Prashanth K, Narayanan K, Asir J, Sheela Devi C, Kumar Amarnath S. The expanding spectrum of human infections caused by Kocuria species: a case report and literature review. Emerg Microbes Infect. 2013 Oct;2(10):e71.

23. What is unique about Staphylococcus lugdunensis in terms of its antibiotic susceptibilities when compared to other coagulase-negative Staphylococcus species?

Answer below.

It is usually methicillin/oxacillin-susceptible.

American Academy of Pediatrics. Coagulase-Negative Staphylococcal Infections. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics. 2021: 692-694

24. Which micronutrient should be withheld from patients with listeriosis?

Answer below.

Iron enhances the pathogenicity of Listeria.

American Academy of Pediatrics. Listeria monocytogenes Infections. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics. 2021: 478-482

25. Describe granulomatosis infantisepticum.

Answer below.

An erythematous rash with small, pale papules characterized histologically by granulomas found in severe newborn Listeria infections.

26. What is the prevalence of stool carriage of Listeria among healthy, asymptomatic adults?

Answer below.

1-5%

27. What is the traditional combination therapy for Listeria infections?

Answer below.

Ampicillin PLUS an aminoglycoside (usually gentamicin)

Bacteremia: 14 days of treatment

Meningitis: 3-4 weeks of treatment

28. What is the treatment of choice for invasive Bacillus cereus?

Answer below.

Vancomycin.

American Academy of Pediatrics. Bacillus cereus Infections and Intoxications. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics. 2021: 219-221

29. What severe organ manifestation is occasionally associated with Bacillus cereus emetic toxin?

Answer below.

Fulminant liver necrosis.

30. What is the preferred antibiotic for Clostridium tetani infection?

Answer below.

Metronidazole decreases the number of vegetative forms of C tetani and is the antimicrobial agent of choice. Penicillin G is an alternative agent. Either should be given alongside tetanus immunoglobulin (TIG), which binds circulating toxin and prevent further progression of disease.

American Academy of Pediatrics. Tetanus. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics. 2021: 750-755

31. What are the 4 overlapping syndromes of Clostridium tetani infection?

Answer below.

Generalized tetanus (lockjaw) consists of trismus and diffuse muscle spasms.

Local tetanus manifests as local muscle spasms contiguous to an infected wound.

Neonatal tetanus (really just generalized tetanus in a newborn infant), mostly characterized by inability to suck or breastfeed, progressing to generalized muscle spasms.

Cephalic tetanus consists of flaccid cranial nerve palsies, sometimes with trismus.

32. What toxin produced by Clostridium tetani is responsible for tetanus?

Answer below.

Tetanospasmin. This exotoxin inhibits normal gamma-aminobutyric acid- and glycine-containing vesicles responsible for inhibiting action on motor and autonomic neurons.

33. Describe the clinical management of tetanus.

Answer below.

- Toxin-neutralizing antibody should be given in the form of tetanus immunoglobulin or IGIV (although it is not approved for this use, and antitetanus antibody concentration is less reliable)

- Existing wounds should be debrided

- Antimicrobial therapy in the form of metronidazole (preferred) or parenteral penicillin G should be given for 7 to 10 days

- Spasms and autonomic instability should be controlled through the use of benzodiazepenes and supportive care

- Subsequent tetanus immunization should be performed during convalescence. Tetanus disease does not necessarily confer immunity.

34. What percentage of healthy, asymptomatic adults have Clostridium septicum detectable in stool samples?

Answer below.

2.8%

Engen RM, Killien EY, Davis JL, Symons JM, Hartmann SM. C septicum Complicating Hemolytic Uremic Syndrome: Survival Without Surgical Intervention. Pediatrics. 2017 Mar;139(3):e20161362.

35. What is the toxin produced in Clostridium septicum sepsis and myonecrosis?

Answer below.

Alpha-toxin may cause tissue necrosis and hemolysis.

Engen RM, Killien EY, Davis JL, Symons JM, Hartmann SM. C septicum Complicating Hemolytic Uremic Syndrome: Survival Without Surgical Intervention. Pediatrics. 2017 Mar;139(3):e20161362.

36. What is the antibiotic of choice against agents of clostridial myonecrosis?

Answer below.

High-dose penicillin G. Alternative agents include clindamycin, metronidazole, meropenem, ertapenem, and chloramphenicol. There is a hypothetical role for combined penicillin G and clindamycin therapy, due to the potential benefit of exotoxin production inhibition by clindamycin.

American Academy of Pediatrics. Clostridial Infections. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics. 2021: 266-277

37. Name some clostridial species associated with myonecrosis.

Answer below.

Clostridium perfringens, Clostridium sordelli, Clostridium septicum, Clostriium novyi.

38. What are the four naturally occurring syndromes of human botulism?

Answer below.

Infant, foodborne, wound, and adult intestinal colonization.

39. What are the most common toxin serotypes found in human botulism? Which ones are more prevalent in infant botulism?

Answer below.

There are a total of 7 toxin types (A-G). The most common in human disease are A, B, E, and occasionally F. Infant botulism is usually due to types A and B.

40. Describe the clinical management of infant and noninfant botulism.

Answer below.

Antitoxin antibodies should be administered immediately. Antitoxin prevents progression of disease, but it does not reverse paralysis, so supportive care will be necessary until the existing toxidrome passes. of note, Human Botulism Immune Globulin for intravenous use (BIG-IV, otherwise known by the brand BabyBIG) is licensed by the FDA for treatment of type A or B infant botulism. Equine-derived heptavalent botulinum antitoxin (BAT) is the only product approved for treatment of noninfant botulism, types A-G. Antimicrobial therapy should be avoided due to the possibility of precipitating toxin release from bacterial cell death, potentially worsening the toxidrome.