Tricuspid valve repair with autologous pericardium in a patient with infective endocarditis

Abstract Infective endocarditis is a rather uncommon disease, but it has significant mortality rates in the pediatric population (5% to 10%). We report a case of an infant patient with multiple vegetation in the tricuspid valve secondary to infective endocarditis caused by Corynebacterium diphtheriae. A tricuspid valvuloplasty was performed with a fenestrated autologous pericardium patch, providing satisfactory outcomes. This technique is simple, innovative, effective, and it could be applied in similar cases.

Adult-onset nasopharyngeal diphtheria: an uncommon but rapidly progressive and potentially fatal infection

@#Nasopharyngeal diphtheria is an acute infectious upper respiratory tract disease caused by toxigenic strains of Corynebacterium diphtheriae. We report a case of a young adult who presented to us with a short history of fever, sore throat, hoarseness of voice and neck swelling. He claimed to have received all his childhood vaccinations and had no known medical illnesses. During laryngoscopy, a white slough (or membrane) was seen at the base of his tongue. The epiglottis was also bulky and the arytenoids were swollen bilaterally. The membrane was sent to the microbiology laboratory for culture. A diagnosis of nasopharyngeal diphtheria was made clinically and the patient was treated with an antitoxin together with erythromycin, while awaiting the culture result. Nevertheless, the patient’s condition deteriorated swiftly and although the laboratory eventually confirmed an infection by toxin-producing C. diphtheriae, the patient had already succumbed to the infection.

Adult Diphteria: Possible Transmission of Corynebacterium diphtheriae from Unvaccinated Child?

@#A case of a toxigenic strain of Corynebacterium diphtheriae in an immunocompetent adult is presented, with the possibility of the adult acquiring the infection from her unvaccinated child. The abovementioned adult is a 29-year-old housewife who was previously immunised with diphtheria, tetanus, and pertussis (DTaP) vaccination in childhood, who presented fever, cough, sore throat, hoarseness of voice, odynophagia, and bilaterally enlarged tonsils. A throat swab confirmed the presence of toxigenic Corynebacterium diphtheriae. The patient was given 80,000 international units (IU) dose of diphtheria antitoxin (DAT) and treated with 2.4 million units (MU) QID intravenous penicillin and oral erythromycin 800 mg twice daily for two weeks. The patient responded well to the treatment and recovered with no cardiovascular or neurotoxicity.

Insights to the diphtheria toxin encoding prophages amongst clinical isolates of Corynebacterium diphtheriae from India

Diphtheria is a dreadful disease caused by Corynebacterium diphtheriae. Lysogenised bacteriophages carrying toxin gene in C. diphtheriae can make the strain toxigenic. However, such phage disseminates the toxin genes to other strains when it undergoes lytic phase. As little is known about the phage diversity in C. diphtheriae in India, the present study was undertaken to investigate the prophages integrated into the genome of 29 clinical isolates of C. diphtheriae using whole-genome shotgun sequencing. Amongst these isolates, 27 were toxigenic, while 2 were non-toxigenic strains. Of the 27 toxigenic strains, all harbored known phages carrying toxin gene and two other phages with unknown function. However, the two non-toxin strains did not harbour any of the phages in the genome. It is imperative to devise prevention strategies that hinder the dissemination of toxin by prophages, as it may increase the complications of diphtheria post-immunisation.

The outcome of resurgence of diphtheria in older children in a tertiary care hospital

Background: Diphtheria is a fatal bacterial infection which affects the mucous membranes of oropharyngeal and nasal cavity, caused by aerobic gram-positive bacteria Corynebacterium diphtheriae. With the advent of universal immunization against diphtheria the incidence of this infectious disease has declined dramatically with few developed nations having eradicated the disease. No large outbreaks have been reported in India in recent times.Methods: In present study, authors reviewed an outbreak of diphtheria in Davangere between the months of June 2017 and July 2018. Case records of children suspected to have diphtheria, admitted to hospitals affiliated to JJM Medical College, Davangere were retrospectively analysed.Results: 15 cases were suspected to have diphtheria on clinical examination. The mean age of presentation was 7.5 years. Fever, sore throat, difficulty in swallowing, neck swelling and patch in oral cavity were the common signs and symptoms. Airway compromise, myocarditis and neurological complications were noted. Antidiphtheritic serum (ADS) was tried in all 15 cases. Case fatality rate was 40%.Conclusions: Diphtheria is a resurgent problem in India. Prompt identification and early appropriate treatment is essential to prevent morbidity and mortality. Strict adherence to the national immunisation schedule should also be emphasized.

Persistence of Corynebacterium diphtheriae in Delhi & National Capital Region (NCR).

Despite the introduction of mass immunization, diphtheria continues to play a major role as a potentially lethal infectious disease in many countries. Delay in the specific therapy of diphtheria may result in death and, therefore, accurate diagnosis of diphtheria is imperative. This study was carried out at National Centre for Disease Control (NCDC), Delhi, India, on samples of suspected diphtheria cases referred from various government hospitals of Delhi and neighbouring areas during 2012-2014. Primary identification of Corynebacterium diphtheriae was done by standard culture, staining and biochemical tests followed by toxigenicity testing by Elek’s test on samples positive for C. diphtheriae. The results showed persistence of toxigenic C. diphtheriae in our community indicating the possibility of inadequate immunization coverage.

Genomic analysis of a nontoxigenic, invasive Corynebacterium diphtheriae strain from Brazil

We report the complete genome sequence and analysis of an invasive Corynebacterium diphtheriae strain that caused endocarditis in Rio de Janeiro, Brazil. It was selected for sequencing on the basis of the current relevance of nontoxigenic strains for public health. The genomic information was explored in the context of diversity, plasticity and genetic relatedness with other contemporary strains.

Corynebacterium diphtheriae putative tellurite-resistance protein (CDCE8392_0813) contributes to the intracellular survival in human epithelial cells and lethality of Caenorhabditis elegans

Corynebacterium diphtheriae, the aetiologic agent of diphtheria, also represents a global medical challenge because of the existence of invasive strains as causative agents of systemic infections. Although tellurite (TeO3^2-) is toxic to most microorganisms, TeO3^2--resistant bacteria, including C. diphtheriae, exist in nature. The presence of TeO3^2--resistance (Te^R) determinants in pathogenic bacteria might provide selective advantages in the natural environment. In the present study, we investigated the role of the putative Te^R determinant (CDCE8392_813gene) in the virulence attributes of diphtheria bacilli. The disruption of CDCE8392_0813 gene expression in the LDCIC-L1 mutant increased susceptibility to TeO3^2- and reactive oxygen species (hydrogen peroxide), but not to other antimicrobial agents. The LDCIC-L1 mutant also showed a decrease in both the lethality of Caenorhabditis elegansand the survival inside of human epithelial cells compared to wild-type strain. Conversely, the haemagglutinating activity and adherence to and formation of biofilms on different abiotic surfaces were not regulated through the CDCE8392_0813 gene. In conclusion, the CDCE8392_813 gene contributes to the Te^R and pathogenic potential of C. diphtheriae.

Evaluation and characterisation of A and B fragments of Corynebacterium diphtheriae toxin towards recombinant diphtheria vaccine.

Background: Diphtheria is a highly communicable disease caused by toxin-producing strains of Corynebacterium diphtheriae. Objectives: To evaluate the efficacy of A and B subunits of diphtheria toxin (DT-A, DT-B) as potential vaccines against C. diphtheriae. A culture of C. diphtheriae (strain PW 8) was grown on Loeffler plates while Lingood medium was used for production of diphtheria toxin (DT). Materials and Methods: DT was purified and digested to obtain pure DT-A and DT-B and detoxified to obtain diphtheria toxin. Four groups of mice were immunised with different antigens (Ag) of C. diphtheriae. Results: The antibody (Ab) titres were significantly increased with immunised groups subsequent to three injections. On the other hand, Ab titres were estimated after the three immunisations and the levels of different Ab isotypes were comparatively measured. The levels of various isotypes immune responses showed variation between immunised groups where the IgG subclasses were significantly increased mainly with DPT immunised group. The IgM and IgA were significantly increased with DT-A more than others. Additionally, the evaluation of the cellular immune responses demonstrated that spleen cells from DPT and DT-A groups gave highly significant proliferative response with production of high levels of IL-2 and IFN-γ (Th1/Th2). Separation and purification of DT gene were performed using polymerase chain reaction (PCR) and sub-cloned in pGEM-T vector, for further studying of recombinant vaccine. Conclusion: Our results showed the possibility to prepare a potent recombinant vaccine containing whole DT gene or DT-A against C. diphtheriae or could be used in treatment of cancer as it give high levels of IL-2 and IFN-γ.

Aspectos fenotípicos e do potencial patogênico de amostra de Corynebacterium diphtheriae isolada de processo de osteomielite em paciente com neoplasia / Phenotypic aspects and pathogenic potential of Corynebacterium diphtheriae strains isolated from cancer patient with osteomyelitis

Além da difteria permanecer endêmica em diversos países, os clínicos e microbiologistas também devem permanecer atentos ao fato de amostras atoxinogênicas de Corynebacterium diphtheriae causarem infecções invasivas, inclusive em pacientesimunocomprometidos e/ou hospitalizados. Um grupo de microrganismos, incluindo C. diphtheriae, tem sido relacionado com quadros de osteomielite. Em casos de câncer, pode ser favorecido o aparecimento de quadros de osteomielite em decorrência de contaminação por via hematogênica, foco infeccioso ou lesão contígua ao osso. Entretanto, ainda são poucas as investigações relativas ao potencial patogênico de cepas atoxinogênicas de C. diphtheriae. No presente estudo, foi descrito o primeiro caso de isolamento de C.diphtheriae subsp. mitis atoxinogênico e do biotipo não fermentador de sacarose (BR5015) de osteomielite em paciente com câncer.O microrganismo foi capaz de expressar os seguintes fatores de virulência: expressão de perfil de aderência misto dos tipos agregativo e difuso (AA-AD) e elevada (11,13%) capacidade de sobrevivência intracitoplasmática em células epiteliais humanas (HEp-2) além da produção de porfirina e de enzimas catalase, nitrato redutase e DNAse. C. diphtheriae atoxinogênico não deve serconsiderado como mero contaminante, uma vez que pode estar direta ou indiretamente relacionado com o estabelecimento e/ou manutenção de processos infecciosos de origens diversas, incluindo osteomielite.

As well diphtheria remaining endemic in several countries, clinicians and microbiologists must also remain alert to the fact that nontoxigenic samples of Corynebacterium diphtheriae are capable of causing invasive infections, especially in hospitalized and/or immunocompromised patients. Patients with cancer are more susceptible to the appearance of cases of osteomyelitisobtained by hematogenic contamination, an infectious focus or by lesions adjacent to bone. Many microorganisms may be related to cases of osteomyelitis, including C. diphtheriae. However, there are still only a low number of investigations into the pathogenic potential of nontoxigenic strains of C. diphtheriae. The present study is the first documented case of isolation of a nontoxigenic C.diphtheriae subsp. mitis of the non sucrose-fermenting biotype (BR5015 strain) from osteomyelitis in the frontal bone of a patient with adenoid cystic carcinoma. The virulence factors tests were as follows: expression of a mixed adherence patterns of aggregativediffuse(AA-DA) types; high (11.13%) ability to survive within HEp-2 cells; DNase, catalase, nitrate-reductase activities. Therefore, nontoxigenic C. diphtheriae should not be merely regarded as a contaminant, since it can be directly or indirectly related to the establishment and/or maintenance of infectious processes, including osteomyelitis.

Fibrinogen binds to nontoxigenic and toxigenic Corynebacterium diphtheriae strains

The production of fibrinous exudates may play an important role in determining the outcome of bacterial infection. Although pseudomembrane formation is a characteristic feature of diphtheria, little is known about the fibrinogen (Fbn)-binding properties of Corynebacterium diphtheriae strains and the influence of the gene that codes for diphtheria toxin (tox gene) in this process. In this study we demonstrated the ability of C. diphtheriae strains to bind to Fbn and to convert Fbn to fibrin. Bacterial interaction with rabbit plasma was evaluated by both slide and tube tests. Interaction of microorganisms with human Fbn was evaluated by both enzyme linked immunosorbent assay (ELISA) and fluorescein isothiocyanate-conjugated (FITC) Fbn binding assays. Nontoxigenic and toxigenic strains formed bacterial aggregates in the presence of plasma in the slide tests. The ability to convert Fbn to a loose web of fibrin in the plasma solution in the tube tests appeared to be a common characteristic of the species, including strains that do not carry the tox gene. Fbn binding to C. diphtheriae strains occurred at varying intensities, as demonstrated by the FITC-Fbn and ELISA binding assays. Our data suggest that the capacity to bind to Fbn and to convert Fbn to fibrin may play a role in pseudomembrane formation and act as virulence determinants of both nontoxigenic and toxigenic strains.

Potential pathogenic role of aggregative-adhering Corynebacterium diphtheriae of different clonal groups in endocarditis

Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years) treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40 percent of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4) and C. diphtheriae subsp gravis (N = 1) displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

Antimicrobial resistance among Brazilian Corynebacterium diphtheriae strains

The increasing problems with multidrug resistance in relation to Corynebacterium, including C. diphtheriae, are examples of challenges confronting many countries. For this reason, Brazilian C. diphtheriae strains were evaluated by the E-Test for their susceptibility to nine antibacterial drugs used in therapy. Resistance (MIC < 0.002; 0.38 µg/ml) to penicillin G was found in 14.8 percent of the strains tested. Although erythromycin (MIC90 0.75 µg/ml) and azithromycin (MIC90 0.064 µg/ml) were active against C. diphtheriae in this study, 4.2 percent of the strains showed decreased susceptibility (MIC 1.0 µg/ml) to erythromycin. Multiple resistance profiles were determined by the disk diffusion method using 31 antibiotics. Most C. diphtheriae strains (95.74 percent) showed resistance to mupirocin, aztreonam, ceftazidime, and/or oxacillin, ampicillin, penicillin, tetracycline, clindamycin, lincomycin, and erythromycin. This study presents the antimicrobial susceptibility profiles of Brazilian C. diphtheriae isolates. The data are of value to practitioners, and suggest that some concern exists regarding the use of penicillin.

Prevalence of diphtheria and tetanus antibodies and circulation of Corynebacterium diphtheriae in São Paulo, Brazil

The introduction of routine vaccination against tetanus and diphtheria in Brazil has decreased the incidence and changed the epidemiology of both diseases. We then investigated the prevalence of Corynebacterium diphtheriae carrier status and diphtheria and tetanus immunity in São Paulo, Brazil. From November 2001 to March 2003, 374 individuals were tested for the presence of C. diphtheriae in the naso-oropharynx and of serum diphtheria and tetanus antibodies. Participants were all healthy individuals without acute or chronic pathologies and they were stratified by age as follows: 0-12 months and 1-4, 5-9, 10-14, 15-24, 25-39, 40-59, and ³60 years. Antibodies were assessed using a double-antigen ELISA. C. diphtheriae species were identified by biochemical analysis and toxigenicity was assessed by the Elek test. For diphtheria, full protection (antibodies ³0.1 IU/mL) was present in 84 percent of the individuals, 15 percent had basic protection (antibodies ³0.01 and <0.1 IU/mL) and 1 percent were susceptible (antibodies <0.01 IU/mL). Full tetanus protection (antibodies ³0.1 IU/mL) was present in 79 percent of the participants, 18 percent had basic protection (antibodies ³0.01 and <0.1 IU/mL) and 3 percent were susceptible (antibodies <0.01 IU/mL). The geometric mean of diphtheria and tetanus antibodies reached the highest values at 5-9 years and decreased until the 40-59-year age range, increasing again in individuals over 60 years. Three participants (0.8 percent) were carriers of C. diphtheriae, all non-toxigenic strains. The present results demonstrate the clear need of periodic booster for tetanus and diphtheria vaccine in adolescents and adults after primary immunization in childhood.

Estudo bacteriológico de cepas de Corynebacterium Diphtheriae isoladas no Estado de São Paulo, Brasil, no período de 1980 a 1986 / Bacteriological study of strains of Corynebacterium Diphtheriae isolated in Säo Paulo State, during the period 1980-1986

Foram analisadas as características de 386 cepas de Corynebacterium diphtheriae isoladas na Seção de Bacteriologia do Instituto Adolfo Lutz, São Paulo, no período de 1980 a 1986. Verificou-se que 58,3% destas cepas foram capazes de fermentar a sacarose. O biótipo mais frequente foi o mitis (52,2%), seguidos pelos biótipos intermedius (26,4%), gravis (9,9%) e de cepas de comportamento atípico (11,7%). Das cepas pertencentes ao biótipo intermedsus, 75,5% foram capazes de fermentar a sacarose. Com relação à produção de toxina, detectada pelo método de Elek, verificou-se que 92,8% das cepas foram poligênicas e que 97,3% das cepas fermentadoras de sacarose produziram toxina (AU).

Corynebacterium diphtheriae isolada de sangue / Corynebacterium diphtheriae isolated of blood

Foi isolado C. diphtheriae de 3 amostras de sangue de um paciente internado no Hospital Emílio Ribas, que não apresentava suspeita clínica de difteria. Analisou-se o aspecto morfológico, comportamento bioquímico e toxigênico destas cepas e verificou-se a presença dos biotipos intermediu8, mitis e mitis variedade belfanti. O comportamento bioquímico foi idêntico para as cepas isoladas, com exceção da presença de nitrato redutase do tipo A nos biotipos intermedius e mitis. Esses dois biotipor mostraram não ser toxigênicos quando testados pelo método de Elek, enquanto o biotipo mitis varo belfanti mostrou-se toxigênico quando empregado o mesmo método. Foi observado não haver variações na sensibilidade dos diferentes antibióticos frente aos agentes antimicrobianos testados (AU).