MICROBIOLOGICAL DIAGNOSIS AND ANTIMICROBIAL TREATMENT OF ACUTE RHEUMATIC FEVER IN PATIENTS WITH PENICILLIN ALLERGY

UDC 616-002.77-036.11-07-08

 

MICROBIOLOGICAL DIAGNOSIS AND ANTIMICROBIAL TREATMENT OF ACUTE RHEUMATIC FEVER IN PATIENTS WITH PENICILLIN ALLERGY

 

Florea Natalia Petru, Doctor of Medical Sciences, Associate Professor,

Department of Public Health, Microbiology and Immunology

State University of Medicine and Pharmacy “N. Testemițanu”

(MD-2004, Moldova, Chişinău, bul. Ştefan cel Mare, 165)

E-mail: natalia.florea@usmf.md

 

Onofrash Daniela Oleg, 6^th year Student, Medicine

State University of Medicine and Pharmacy “N. Testemițanu”

(MD-2004, Moldova, Chişinău, bul. Ştefan cel Mare, 165)

E-mail: daniela.onofras2@gmail.com

 

Abstract. Streptococcus pyogenes, which is beta-hemolytic. Once in the body, streptococci can cause tonsillitis, pharyngitis with lymphadenitis, scarlet fever, pneumonia, wound and skin infections, sepsis and endocarditis. Complications of GABHS infection include rheumatic fever and glomerulonephritis. Acute rheumatic fever is an inflammatory disease that can affect the heart, joints and skin. Rheumatism most often occurs in childhood and adolescence, adults suffer much less often. Women get sick three times more often than men. Streptococci are usually cultivated on blood agar media, at a temperature of 35°C to 37°C in the presence of 5% CO2 or under anaerobic conditions. Penicillin is the drug of choice for GABHS infection, but in patients with penicillin allergy, when penicillin and beta-lactams are contraindicated, options include: Azithromycin 500 mg, Cephalexin 500 mg, Cefadroxil 500 mg, Clarithromycin 250 mg, Clindamycin 600 mg.

Keywords: Streptococcus pyogenes, rheumatic fever, Penicillin.

 

Actuality: A thorough literature search identified relevant studies was conducted throughout the period 1990-2015 from all continents. The overall mean incidence of first attack (ARF) was 19 per 100,000 population [3].

Group A beta-hemolytic streptococci GABHS, the most important pathogen in the group of streptococci is Streptococcus pyogenes, which is beta-hemolytic. Once in the body, streptococci can cause tonsillitis, pharyngitis with lymphadenitis, scarlet fever, pneumonia, wound and skin infections, sepsis and endocarditis. Complications of GABHS infection include rheumatic fever and glomerulonephritis. Acute rheumatic fever is an inflammatory disease that can affect the heart, joints and skin. Most often, the disease begins two to four weeks after a streptococcal throat infection. Rheumatism most often occurs in childhood and adolescence, adults suffer much less often. Women get sick three times more often than men. Pathogenic beta-hemolytic streptococci produce antigens: streptolysin O and streptolysin S. The first affects heart cells, the second mainly affects the joints. The immune system produces antistreptolysin antibodies to antigens, which attack not only them, but also the corresponding tissue type. As a result, an autoimmune component is added to the inflammatory process caused by exposure to streptococcal antigens, which significantly worsens the course of the disease. Acute poststreptococcal glomerulonephritis is a syndrome that develops as a complication of pharyngitis or skin infection, caused by a limited number of nephrogenic strains of GABHS protein serotypes M 12 and 49. After a throat or skin infection caused by one of these strains, approximately 10-15% of patients develop acute glomerulonephritis [2].

Materials and methods:

Streptococci are usually grown on blood agar media. This method allows the determination of β-hemolysis. Optimal incubation conditions for streptococcal strains include temperatures from 35°C to 37°C in the presence of 5% CO2 or under anaerobic conditions. To identify S. pyogenes preemptively, cultures can be tested for bacitracin susceptibility and PYR activity. The PYR test is a rapid colorimetric method often used to distinguish S. pyogenes from other β-hemolytic streptococci. Definitive diagnosis of S. pyogenes should include a positive Lancefield group A antigen test or species identification by automated methods such as MALDI TOF or Vitek. If no growth is observed within 48 hours, the result can be confirmed negative.

Penicillin is the drug of choice for pharyngeal GABHS infection and is therefore usually prescribed to treat streptococcal infections. No GABHS isolates have shown resistance to penicillin. However, some strains of streptococci are resistant to penicillin in vitro, with significantly reduced bactericidal effect of penicillin. Resistance to macrolides is increasing, so antibiotic susceptibility testing is recommended when using drugs from this group.

In patients with penicillin allergy and recent antibiotic use, third-generation cephalosporins should be considered as alternative drugs for the treatment of acute streptococcal otitis media. Narrow-spectrum oral cephalosporins such as Cephalexin, Cefadroxil are also effective and may be used if patients have an anaphylactic reaction to penicillin.

When penicillin and beta-lactams are contraindicated, options include:

Azithromycin 500 mg (15 mg/kg for children) orally once daily for 5 days.

Cephalexin 500 mg (20 mg/kg for children) orally every 12 hours for 10 days.

Cefadroxil 500 mg (15 mg/kg for children) orally every 12 hours for 10 days.

Clarithromycin 250 mg (7.5 mg/kg for children) orally every 12 hours for 10 days.

Clindamycin 600 mg (7 mg/kg for children) orally every 8 hours, 10 days [1].

 

Conclusions:

1. In 2020, an average of 35 million cases of rheumatic disease were recorded globally.

2. The main role in the etiology of rheumatic fever is played by Group A beta-hemolytic Streptococcus, the most important pathogen being Streptococcus pyogenes.

3. Current microbiological diagnostic methods include: the classical bacteriological method, MALDI TOF, Vitek, PCR and others.

4. Antimicrobial treatment in rheumatic fever, in patients with penicillin allergy, when penicillin and beta-lactams are contraindicated, options include:

Azithromycin 500 mg, Cephalexin 500 mg, Cefadroxil 500 mg, Clarithromycin 250 mg, Clindamycin 600 mg [2].

5. Primary prevention of rheumatic fever aims to reduce the risk of streptococcal infection. Cultures should be done to confirm negative results, at least in children. Medical supervision of children whose parents suffer from rheumatism or often suffer from streptococcal infections.

 

REFERENCES

1. Luo, R., Sickler, J., Vahidnia, F., Lee, Y-C., Frogner, B., Thompson, M. Diagnosis and treatment of group A streptococcal pharyngitis in the United States, 2011–2015. BMC Infectious Diseases. 2019 Feb 26; 19 (1):193. [ PMC free article ] [ PubMed ].
2. Tanz, R.R., Ranniger, E.J., Rippe, J.L., Dietz, R.L., Oktem, C.L., Lowmiller, C.L., Shulman, S.T. Highly sensitive molecular assay for group A streptococci overestimates carriers and may impact antimicrobial stewardship in the outpatient setting. J Pediatric Infectious Diseases. 2019 Aug;38(8):769–774. [ PubMed ].
3. Watkins, D.A., Johnson, C.O., Colquhoun, S.M., et al: Global, regional, and national burden of rheumatic heart disease, 1990–2015. N Engl J Med 377:713–722, 2017. doi: 10.1056/NEJMoa1603693.

 

REFERENCES

1.   Luo R., Sickler J., Vahidnia F., Lee Y-C., Frogner B., Thompson M. Diagnosis and treatment of group A streptococcal pharyngitis in the United States, 2011–2015. BMC Infectious Diseases. 2019 Feb 26; 19 (1):193. [ PMC free article ] [ PubMed ].

2.   Tanz R.R., Ranniger E.J., Rippe J.L., Dietz R.L., Oktem C.L., Lowmiller C.L., Shulman S.T. Highly sensitive molecular assay for group A streptococci overestimates carriers and may impact antimicrobial stewardship in the outpatient setting. J Pediatric Infectious Diseases. 2019 Aug;38(8):769–774. [ PubMed ].

3.   Watkins D.A., Johnson C.O., Colquhoun S.M., et al: Global, regional, and national burden of rheumatic heart disease, 1990–2015. N Engl J Med 377:713–722, 2017. doi: 10.1056/NEJMoa1603693.

 

Материал поступил в редакцию 31.03.25

 

 

МИКРОБИОЛОГИЧЕСКАЯ ДИАГНОСТИКА И АНТИМИКРОБНОЕ ЛЕЧЕНИЕ ОСТРОЙ РЕВМАТИЧЕСКОЙ ЛИХОРАДКИ У БОЛЬНЫХ С АЛЛЕРГИЕЙ НА ПЕНИЦИЛЛИН

 

Флоря Наталья Петру, доктор медицинских наук, доцент, дисциплина микробиологии и иммунологии

ГMФУ имени “Н Тестемицану”

(MD-2004, Молдова, Кишинев, бул. Штефана чел Маре, 165)

E-mail: natalia.florea@usmf.md

 

Онофраш Даниэла, студент 6 курса, Медицина

ГMФУ имени “Н Тестемицану”

(MD-2004, Молдова, Кишинев, бул. Штефана чел Маре, 165)

E-mail: daniela.onofras2@gmail.com

 

Аннотация. Streptococcus pyogenes, обладающий бета-гемолитическим действием. Попадая в организм, стрептококки могут вызывать тонзиллит, фарингит с лимфаденитом, скарлатину, пневмонию, раневые и кожные инфекции, сепсис и эндокардит. Осложнения инфекции БГСА включают ревматическую лихорадку и гломерулонефрит. Острая ревматическая лихорадка – воспалительное заболевание, которое может поражать сердце, суставы и кожу. Ревматизм возникает чаще всего в детском и подростковом возрасте, взрослые болеют значительно реже. Женщины болеют в три раза чаще мужчин. Стрептококки обычно выращивают на кровяном агаре при температуре от 35°C до 37°C в присутствии 5% CO2 или в анаэробных условиях. Пенициллин является препаратом выбора при инфекции БГСА, но у пациентов с аллергией на пенициллин, когда пенициллин и бета-лактамы противопоказаны, варианты включают: Азитромицин 500 мг, Цефалексин 500 мг, Цефадроксил 500 мг, Кларитромицин 250 мг, Клиндамицин 600 мг.

Ключевые слова: Streptococcus pyogenes, ревматизм, пенициллин.