Beta-lactam antibiotics and viridans group streptococci / Antibióticos beta-lactámicos y estreptococos grupo viridans

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).

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).

Beta-lactam antibiotics and viridans group streptococci.

The aim of this review is to present an update on the susceptibility of viridans group streptococci (VGS) to ß-lactam antimicrobials, with emphasis on the Argentinean scenario. VGS are a heterogeneous group including five groups of species, each one exhibiting peculiar susceptibility patterns to penicillin (PEN). Species of the Streptococcus mitis group are frequently nonsusceptible to PEN. PEN resistance is associated with changes in PEN-binding proteins. In Argentina, one to two thirds of VGS are nonsusceptible to PEN. Third generation cephalosporins and carbapenems are currently more effective in vitro than PEN against VGS. Mortality was associated to nonsusceptibility to PEN in at least two studies involving patients with bacteremia caused by VGS. Treatment of endocarditis due to VGS should be adjusted/to the PEN susceptibility of the isolates. Vancomycin may be an alternative choice for treating endocarditis caused by PEN-resistant isolates (MIC≥4µg/ml).

Epidemiology of Invasive Infections Caused by Streptococcus agalactiae in Argentina.

In recent years, an increase in the number of cases of invasive infections due to Streptococcus agalactiae (group B Streptococcus [GBS]) in adults has been reported. During 2014 and 2015, a multicentric, observational, and prospective study, including 40 health centers, was developed to describe the phenotypic and genotypic characteristics of GBS isolates circulating in Argentina and to analyze the clinical and demographic characteristics of patients with invasive infections. We recovered 162 invasive (GBSi) isolates from adult patients (n = 130, 80.2%), neonates (n = 24, 15%), and children below 18 years of age (n = 8, 4.8%), and colonizing (GBSc) isolates were recovered in prenatal GBS screening. GBS infection in adults was associated with underlying diseases, mainly diabetes mellitus. All isolates were penicillin susceptible. Resistance rates to erythromycin (25%) and clindamycin (26%) among the GBSc isolates were significantly higher than those from GBSi strains (17.3% and 16.1%, respectively); by contrast, levofloxacin resistance was significantly higher in GBSi isolates (14.8% vs. 7%). Serotype Ia was the most frequent in neonates and Ib was most frequent in adults. Serotypes Ia and III were prevalent in GBSc isolates. The increase of levofloxacin resistance was associated with the presence of a serotype Ib clone. This work emphasizes the need for GBS infection surveillance studies to implement correct treatments and adequate prevention strategies.

Estreptococos del grupo Streptococcus anginosus Parte IIIb. Infecciones en localizaciones diferentes de las de cabeza y cuello / Streptococcus anginosus group. Part IIIb. Other than head and neck infections

Resumen Las bacterias del grupo Streptococcus anginosus (EGA) son colonizantes habituales de las mucosas orofaríngea, intestinal y genitourinaria, pero, cada vez más frecuentemente, son reconocidas como patógenos humanos. En esta parte III se describen las tendencias de los EGA a la producción de distintas patologías humanas. Por su extensión debió ser desdoblada a su vez en otras dos partes (IIIa y IIIb). Es ampliamente conocida su capacidad de formar abscesos en órganos sólidos, especialmente abscesos cerebrales, pulmonares y hepáticos. También producen sinusitis, empiemas y colecciones en piel y tejidos blandos, huesos, articulaciones, etc. Se han encontrado asociados con infecciones urinarias, vaginitis aeróbica y con exacerbaciones pulmonares en pacientes con fibrosis quística y con enfermedad pulmonar obstructiva crónica. Producen también infecciones posteriores a mordeduras humanas, infecciones diseminadas, bacteriemia sin foco aparente y, en menor medida, endocarditis infecciosas, generalmente complicadas con abscesos perivalvulares. Esta parte IIIb está focalizada en las infecciones que no comprometen la cabeza y el cuello.

Abstract Streptococcus anginosus (SGA) group streptococci are common colonizers of the oropharyngeal, intestinal, and genitourinary mucosa, but they are increasingly recognized as human pathogens. In this part III, tendencies of the EGA to the production of different human pathologies are described. Due to its length, it had to be divided into two other parts (IIIa and IIIb). Its ability to form abscesses in solid organs, especially brain, lung and liver abscesses, is widely known. They also cause sinusitis, empyema and collections in skin and soft tissues, bones, joints, etc. They have been found associated with urinary tract infections, aerobic vaginitis and with pulmonary exacerbations in patients with cystic fibrosis and chronic obstructive pulmonary disease. They also cause infections after human bites, disseminated infections, bacteremia without apparent focus and, to a lesser extent, infective endocarditis, generally complicated by perivalvular abscesses. This part IIIb is focused on other than head and neck infections.

Resumo As bactérias do grupo Streptococcus anginosus (EGA) são colonizadores comuns da mucosa orofaríngea, intestinal e geniturinária, mas são cada vez mais reconhecidos como patógenos humanos. Nesta parte III são descritas as tendências do EGA à produção de diferentes patologias humanas. Devido ao seu comprimento, teve que ser dividido em duas outras partes (IIIa e IIIb). Sua capacidade de formar abcessos em órgãos sólidos, principalmente cérebro, pulmão e fígado, é amplamente conhecida. Eles também causam sinusite, empiema e coleções na pele e tecidos moles, ossos, articulações, etc. Eles foram encontrados associados à infecções urinárias, vaginite aeróbia e às exacerbações pulmonares em pacientes com fibrose cística e doença pulmonar obstrutiva crônica. Também causam infecções após picadas humanas, infecções disseminadas, bacteremia sem origem aparente e, em menor grau, endocardite infecciosa, geralmente complicada por abscessos perivalvulares. Seu papel na faringite é controverso, embora algumas das subespécies possam estar envolvidas em tais infecções. Seu potencial carcinogênico também é postulado pela associação com carcinomas orofaríngeos, gástricos ou esofágicos. Esta parte IIIb enfoca infecções em diferentes locais da cabeça e pescoço.

Resistance to ß-lactams in Streptococcus pneumoniae.

Streptococcus pneumoniae is an important causal agent of pneumonia, meningitis, sepsis, bacteremia, and otitis media. Penicillin resistance rates in S. pneumoniae have remained stable in Argentina in the last years. In the late '90s more isolates with MIC of penicillin ≥2µg/ml were observed; however, their frequency has decreased in recent years. The phenotypic expression of penicillin resistance is due to a modification in penicillin-binding proteins associated with a mosaic structure in the coding genes. The expansion of successful resistant clones varies among the different regions and is influenced by the use of antibiotics, vaccines, particularly conjugated ones, as well as population density. Parenteral treatment with high doses of penicillin G continues to be effective for the treatment of pneumonia and bacteremia, oral aminopenicillins for otitis media and sinusitis and third generation cephalosporins for meningitis.

Estreptococos del grupo Streptococcus anginosus Parte IIIa. Epidemiología e infecciones de cabeza y cuello / Streptococcus anginosus group. Part IIIa. Epidemiology and head and neck infections

Resumen Los estreptococos del grupo Streptococcus anginosus (EGA) son colonizantes habituales de las mucosas orofaríngea, intestinal y genitourinaria, pero, cada vez más frecuentemente, son reconocidos como patógenos humanos. En esta parte IIIa se describen la epidemiología de las infecciones por EGA y las características de las localizadas en cabeza y cuello. Es ampliamente conocida su capacidad de formar abscesos; en particular en la zona de cabeza y cuello se destacan los abscesos odontogénicos, los periorbitales y los cerebrales. También producen sinusitis, infecciones oculares, abscesos epidurales, síndrome de Lemierre, empiemas subdurales y colecciones en piel y tejidos blandos y huesos del cráneo. Su rol en la faringitis es controvertido aunque algunas de las subespecies podrían estar involucradas en ese tipo de infecciones. También se postula su potencial cancerígeno dada su asociación con carcinomas orofaríngeos, gástricos o esofágicos.

Abstract Streptococcus anginosus group (SAG) organisms are common colonizers of the oropharyngeal, intestinal, and genitourinary mucosa, but are increasingly recognized as human pathogens. This part IIIa describes the epidemiology of SAG infections and the characteristics of those located in the head and neck. Its ability to form abscesses is widely known, particularly, in the head and neck area; odontogenic, periorbital and brain abscesses stand out. They also cause sinusitis, eye infections, epidural abscesses, Lemierre's syndrome, subdural empyemas, and collections in the skin and soft tissues and bones of the skull. Its role in pharyngitis is controversial, although some of the subspecies could be involved in such infections. Its carcinogenic potential is also postulated given its association with oropharyngeal, gastric or esophageal carcinomas..

Resumo Os estreptococos do grupo Streptococcus anginosus (EGA) são colonizadores comuns da mucosa orofaríngea, intestinal e geniturinária, mas são cada vez mais frequentemente reconhecidos como patógenos humanos. Esta parte IIIa descreve a epidemiologia das infecções por EGA e as características daquelas localizadas na cabeça e no pescoço. Sua capacidade de formar abscessos é amplamente conhecida, principalmente, na região da cabeça e pescoço, destacando-se os abscessos odontogênicos, os periorbitais e os cerebrais. Eles também causam sinusite, infecções oculares, abscessos epidurais, síndrome de Lemierre, empiemas subdurais e coleções em pele e tecidos moles, e ossos do crânio. Seu papel na faringite é controverso, embora algumas das subespécies possam estar envolvidas em tais infecções. Seu potencial carcinogênico também é postulado pela associação com carcinomas orofaríngeos, gástricos ou esofágicos.

[Development of a simple medium for the selective isolation of bacteria belonging to the Streptococcus anginosus group]. / Desarrollo de un medio simple para el aislamiento selectivo de bacterias del grupo Streptococcus anginosus.

Bacteria of the Streptococcus anginosus group (SAG) have recently been recognized as contributors of bronchopulmonary disease in cystic fibrosis (CF). Routine detection and quantification are limited by current CF microbiology protocols. The development of the CHROMagar™ StrepB chromogenic medium modified by the addition of plasma, nalidixic acid, colistin and sulfadiazine to make it selective for SAG bacteria is described. This medium could be used as a diagnostic tool to detect SAG in respiratory samples from patients suffering from chronic lung disease.

Estreptococos del grupo Streptococcus anginosus Parte II. Patogenia y sensibilidad a los antibióticos / Streptococcus anginosus group. Part II. Pathogenesis and antimicrobial susceptibility / Estreptococos do grupo Streptococcus anginosus. Parte II. Patogênese e sensibilidade aos antibióticos

Resumen En esta segunda parte de la actualización sobre estreptococos del grupo Streptococcus anginosus (EGA) se describen sus factores de virulencia y su sensibilidad a los antibióticos. Los EGA, pertenecientes al grupo de los estreptococos viridans (EGV), son colonizantes habituales de las mucosas orofaríngea, intestinal y genitourinaria, pero, cada vez más frecuentemente, son reconocidos como patógenos humanos. Entre sus factores de virulencia se han descripto enzimas como la hialuronidasa, la condroitín sulfatasa y las nucleasas (DNasas y RNasas). En algunas cepas se han detectado también exoenzimas superantigénicas homólogas a las de Streptococcus pyogenes. Es notable el rol de las hemolisinas (citolisinas), como la estreptolisina O y la intermedilisina, específica de Streptococcus intermedius, una de las tres especies que conforman el grupo. Los EGA presentan bajos porcentajes de no sensibilidad a los beta-lactámicos (penicilina: 0-15%, cefotaxima: 0-3% y carbapenemes: 0-3%) con muy pocas excepciones y muy pocos aislados resistentes. En cambio, son naturalmente resistentes al metronidazol y a los nitrofuranos. Se han informado porcentajes elevados de resistencia a macrólidos, clindamicina y tetraciclina (en algunos casos hasta más de 50%). La resistencia a las fluoroquinolonas es variable, pero muy baja para levofloxacina. Los EGA generalmente son sensibles a vancomicina y/o teicoplanina con concentraciones inhibitorias mínimas (CIM)≤1 μg/mL, aunque es destacable la descripción de unos pocos aislados con sensibilidad disminuida a vancomicina, uno de ellos portador del gen vanG. La resistencia a otros antibióticos se observó solo en forma esporádica.

Abstract This second part of the review about Streptococcus anginosus group streptococci (SAG) describes their virulence factors and their antimicrobial susceptibility. SAG are common colonizers of the oropharyngeal, intestinal, and genitourinary mucosa, but are increasingly recognized as human pathogens. Among their virulence factors, enzymes such as hyaluronidase, chondroitin sulfatase and nucleases (DNases and RNases) have been described. Superantigenic exoenzymes homologous to those of Streptococcus pyogenes have also been detected in some strains. The role of hemolysins (cytolysins) is notable, and specifically that of intermedilysin in Streptococcus intermedius, one of the three species of the group. SAG present low percentages of non-sensitivity to beta-lactams (penicillin: 0-15%, cefotaxime: 0 - 3% and carbapenems: 0-3%) with very few exceptions and very few resistant isolates. Instead, they are naturally resistant to metronidazole and nitrofurans. High percentages of resistance to macrolides, clindamycin and tetracycline have been reported (in some cases up to more than 50%). Fluoroquinolone resistance is variable, but it is very low for levofloxacin. SAG are generally susceptible to vancomycin and/or teicoplanin with minimal inhibitory concentrations (MICs)≤1 μg/mL, although the isolation of a few isolates with decreased sensitivity to vancomycin, one of them carrying the vanG gene, is notable. Resistance to other antibiotics was observed only sporadically.

Resumo Esta segunda parte da revisão sobre estreptococos do grupo Streptococcus anginosus (EGA) descreve seus fatores de virulência e sensibilidade aos antibióticos. Os EGAs, pertencentes ao grupo dos estreptococos viridans (EGV), são colonizadores comuns das mucosas orofaríngea, intestinal e geniturinária, mas são cada vez mais reconhecidos como patógenos humanos. Entre seus fatores de virulência, foram descritas enzimas como hialuronidase, condroitina sulfatase e nucleases (DNases e RNases). Exoenzimas superantigênicas homólogas às de Streptococcus pyogenes também foram detectadas em algumas cepas. O papel das hemolisinas (citolisinas), como a estreptolisina O e a intermedilisina, específica de Streptococcus intermedius, uma das três espécies que compõem o grupo é notável. Os EGAs apresentam baixo percentual de não sensibilidade aos betalactâmicos (penicilina: 0-15 %, cefotaxima: 0-3% e carbapenemas: 0-3%) com muito poucas exceções e muito poucos isolados resistentes. Em vez disso, são naturalmente resistentes ao metronidazol e aos nitrofuranos. Foram relatados altos percentuais de resistência aos macrólidos, clindamicina e tetraciclina (em alguns casos, até mais de 50%). A resistência às fluoroquinolonas é variável, mas muito baixa para a levofloxacina. Os EGAs são geralmente sensíveis à vancomicina e/ou teicoplanina com concentrações inibitórias mínimas (CIM)≤1 μg/ mL, embora seja notável a descrição de alguns isolados com sensibilidade reduzida à vancomicina, um deles portador do gene vanG. Resistência a outros antibióticos foi observada apenas esporadicamente.