Antibióticos beta-lactámicos y estreptococos grupo viridans

Lopardo, Horacio A.; Vigliarolo, Laura; Bonofiglio, Laura; Gagetti, Paula; Gabarrot, Gabriela García; Kaufman, Sara; Mollerach, Marta; Toresani, Inés; Specht, Martha von; Lopardo, Horacio A.; Vigliarolo, Laura; Bonofiglio, Laura; Gagetti, Paula; Gabarrot, Gabriela García; Kaufman, Sara; Mollerach, Marta; Toresani, Inés; Specht, Martha von

doi:10.1016/j.ram.2022.06.004

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Revista argentina de microbiología

versión impresa ISSN 0325-7541versión On-line ISSN 1851-7617

Rev. argent. microbiol. vol.54 no.4 Ciudad Autónoma de Buenos Aires dic. 2022 Epub 01-Dic-2022

http://dx.doi.org/10.1016/j.ram.2022.06.004

SPECIAL ARTICLE

Beta-lactam antibiotics and viridans group streptococci

Antibióticos beta-lactámicos y estreptococos grupo viridans

Horacio A. Lopardo¹

Laura Vigliarolo¹

Laura Bonofiglio¹

Paula Gagetti¹

Gabriela García Gabarrot¹

Sara Kaufman¹

Marta Mollerach¹

Inés Toresani¹

Martha von Specht¹

^¹ a Grupo STREP de la Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas (SADEBAC), División de la Asociación Argentina de Microbiología, Argentina. 2 b Cátedra de Microbiología Clínica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Provincia de Buenos Aires, Argentina. 3 c Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Microbiología, Ciudad Autónoma de Buenos Aires, Argentina d CONICET, Argentina. 4 e Servicio Antimicrobianos, Departamento de Bacteriología, Instituto Nacional de Enfermedades Infecciosas (INEI), ANLIS «Dr. Carlos G. Malbrán», Ciudad Autónoma de Buenos Aires, Argentina. 5 f Programa de Desarrollo de las Ciencias Básicas (PEDECIBA), Universidad de la República, Montevideo, Uruguay g Sección Microbiología Clínica, División Laboratorio, Hospital Juan A. Fernández, Ciudad Autónoma de Buenos Aires, Argentina h Cátedra de Bacteriología, Facultad de Ciencias Bioquímicas, Universidad Nacional de Rosario, Rosario, Provincia de Santa Fe, Argentina. 6 i Laboratorio de Bacteriología, Hospital Provincial de Pediatría «Dr. F. Barreyro», Posadas, Misiones, Argentina j Departamento de Microbiología, Facultad de Ciencias Exactas Químicas y Naturales, Universidad Nacional de Misiones, Posadas, Misiones, Argentina.

Abstract

The aim of this review is to present an update on the susceptibility of viridans groupstreptococci (VGS) to -lactam antimicrobials, with emphasis on the Argentinean scenario. VGSare a heterogeneous group including five groups of species, each one exhibiting peculiar sus-ceptibility patterns to penicillin (PEN). Species of the Streptococcus mitis group are frequentlynonsusceptible to PEN. PEN resistance is associated with changes in PEN-binding proteins. InArgentina, one to two thirds of VGS are nonsusceptible to PEN. Third generation cephalosporinsand carbapenems are currently more effective in vitro than PEN against VGS. Mortality was asso-ciated to nonsusceptibility to PEN in at least two studies involving patients with bacteremiacaused by VGS. Treatment of endocarditis due to VGS should be adjusted/to the PEN suscepti-bility of the isolates. Vancomycin may be an alternative choice for treating endocarditis causedby PEN-resistant isolates (MIC 4 g/ml).

KEYWORDS: Viridans groupstreptococci;Lactams; Resistance; Penicillin bindingproteins ;Endocarditis

Resumen

El objetivo de esta revisión es presentar una actualización sobre la sensibilidad de los estreptococos del grupo viridans (EGV) a los antimicrobianos p-lactámicos, con énfasis en el escenario argentino. Los EGV son un grupo heterogéneo que incluye cinco grupos de especies, y cada una presenta su patrón especial de sensibilidad a la penicilina (PEN). Las especies del grupo Streptococcus mitis, con mayor frecuencia, no son sensibles a la PEN. La resistencia a la PEN se asocia con cambios de las proteínas ligadoras de PEN. En la Argentina, de uno a dos tercios de los EGV no son sensibles a la PEN. Las cefalosporinas de tercera generación y los carbapenemes son actualmente más eficaces in vitro que la PEN contra los EGV. La mortalidad se asoció con la no sensibilidad a la PEN en al menos dos estudios de pacientes con bacteriemia por EGV. El tratamiento de las endocarditis por EGV debe ajustarse según la sensibilidad a la PEN de los aislados. La vancomicina podría ser una elección alternativa para el tratamiento de las endocarditis por cepas resistentes a PEN (CIM >4 ^g/ml).

PALABRAS CLAVE: Estreptococos delgrupo viridans; Lactámicos ;Resistencia; Proteínas ligadoras depenicilina ;Endocarditi

Introduction

Viridans group streptococci (VGS) are a heterogeneous group that includes five groups of species: Streptococcus mitis group, Streptococcus salivarius group, Streptococcus anginosus group (sometimes still referred to as "Streptococcus milleri”, which is not a validly published denomination), Streptococcus mutans group, and Streptococcus bovis group (frequently referred to as group D streptococci)²³.

Despite belonging to the S. mitis group because of its molecular similarity, S. pneumoniae is usually described separately due to its distinguishing clinical and epidemi-ological impact, and will not be covered in the present review.

Identifying them at the species or subspecies level is very difficult using current biochemical methods, includ-ing API 20 Strep, Vitek 2, Phoenix and similar automated methods. Moreover, mass spectrometry and some sequenc-ing methods may also misidentify some VGS species or subspecies2.

The multilocus sequence analysis (MLSA), employing seven house-keeping gene sequences, has demonstrated its ability to identify VGS at the species level7. However, there are still problems to identify some species such as S. mitis and S. oralis, and also to differentiate them from S. pneumoniae due to their frequent intra- and interspecies gene transfer of mosaic genes¹⁹.

The aim of this review was to present an update of p-lactam resistance among VGS, emphasizing the Argentinean experience. It is not a systematic review but a report on information obtained from selected studies and guidelines.

Human diseases associated with viridans group streptococciVGS are an important part of the commensal microbiota of the human oropharyngeal cavity, vagina and gastrointestinal tract. However, they are the causative microorganisms of up to 40-60% of cases of native-valve endocarditis27, and also of 16% of cases of prosthetic-valve endocarditis26. Their role in the bacteremia of neutropenic patients, especially those with hematologic malignancies, is a matter of growing concern^28,31.

Table 1: VGS Species groups and their most frequently associated pathologies.

An association of S. bovis group with colorectal carcinoma has been largely reported since the 50s. Despite being especially related to Streptococcus gallolyticus subsp. gallolyticus, when isolated from clinical samples, it is advisable to report S. bovis at group level in order to promote colorectal cancer screening11.

S. anginosus group is associated with different types of purulent collections, including brain, liver and pulmonary abscesses5,6. These and other associated pathologies are shown in Table 1.

Conclusions

The viridans group is a heterogeneous species group, each one with its characteristic susceptibility to p-lactams. PEN nonsusceptibility is due to modifications of the PBPs, espe-cially those of higher molecular mass. Reduced susceptibility to PEN is more frequent among isolates of S. mitis and to a lesser extent S. salivarius, than among isolates of S. anginosus or S. bovis groups. According to their relative frequency, PNS ranges from 20 to 60%. Third generation cephalosporins and carbapenems are currently more effec-tive in vitro than PEN against VGS. The main clinical impact of PEN resistance occurs in endocarditis, where it seems to play an important role in relation to mortality.

Ethical responsibilitiesNot applicable.

FundingNone declared.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Acknowledgment

Authors are grateful to Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas (SADEBAC), a division of Asociación Argentina de Microbiología for its permanent encouragement and support.

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Received: February 14, 2022; Accepted: June 24, 2022

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