Donor-derived TB after kidney transplantation: a case report / TB derivada do doador após transplante renal: um relato de caso

Abstract Introduction: Tuberculosis (TB) is a possible serious complication of solid organ transplantation, associated with high mortality and morbidity. Post-transplant TB has varied pathogenesis with many approaches to its prevention, which is the most important way to reduce its incidence. Treatment of TB in organ recipients is challenging because of drug toxicity and interaction with immunosuppressants. Case report: an 18-year-old woman that underwent kidney transplantation from a deceased donor and was discharged with fair renal function was readmitted at 37th postoperative day with fever. CT showed signs of miliary TB and fluid collection besides graft fistulization through the skin. The patient presented positive BAAR in the drained fluid and Koch's bacillus in the urine. She was treated with a four-drug regimen (rifampicin, isoniazid, pyrazinamide, and etambutol), with great response and preserved graft function. We were informed that the recipient of the contralateral kidney also presented post-transplant TB, implying in a donor-derived origin. Conclusion: TB is an important differential diagnosis for infectious complications in patients after solid-organ transplantation, especially in endemic regions. Its initial clinical presentation can be unspecific and it should be suspected in the presence of fever or formation of fluid collections. The suspicion of TB is the key to early diagnosis and satisfactory outcomes in post-transplant TB.

Resumo Introdução: A tuberculose (TB) é uma possível complicação grave do transplante de órgãos sólidos, associada à alta mortalidade e morbidade. A TB pós-transplante tem patogênese variada com muitas abordagens para sua prevenção, que é a forma mais importante de reduzir sua incidência. O tratamento da TB em receptores de órgãos é um desafio devido à toxicidade dos medicamentos e à interação com imunossupressores. Relato de caso: uma mulher de 18 anos que foi submetida a transplante renal de um doador falecido e recebeu alta com função renal adequada foi readmitida no 37º dia de pós-operatório com febre. A TC mostrou sinais de TB miliar e coleção de fluidos além de fistulização do enxerto através da pele. A paciente apresentou BAAR positivo no fluido drenado e bacilo de Koch na urina. Ela foi tratada com um esquema de quatro medicamentos (rifampicina, isoniazida, pirazinamida e etambutol), com ótima resposta e função de enxerto preservada. Fomos informados de que o receptor do rim contralateral também apresentou TB pós-transplante, implicando em uma origem derivada do doador. Conclusão: A TB é um importante diagnóstico diferencial para complicações infecciosas em pacientes após transplante de órgãos sólidos, especialmente em regiões endêmicas. Sua apresentação clínica inicial pode não ser específica e deve ser suspeitada na presença de febre ou formação de coleções de fluidos. A suspeita de TB é a chave para o diagnóstico precoce e desfechos satisfatórios na TB pós-transplante.

Donor-derived TB after kidney transplantation: a case report.

INTRODUCTION: Tuberculosis (TB) is a possible serious complication of solid organ transplantation, associated with high mortality and morbidity. Post-transplant TB has varied pathogenesis with many approaches to its prevention, which is the most important way to reduce its incidence. Treatment of TB in organ recipients is challenging because of drug toxicity and interaction with immunosuppressants. CASE REPORT: an 18-year-old woman that underwent kidney transplantation from a deceased donor and was discharged with fair renal function was readmitted at 37th postoperative day with fever. CT showed signs of miliary TB and fluid collection besides graft fistulization through the skin. The patient presented positive BAAR in the drained fluid and Koch's bacillus in the urine. She was treated with a four-drug regimen (rifampicin, isoniazid, pyrazinamide, and etambutol), with great response and preserved graft function. We were informed that the recipient of the contralateral kidney also presented post-transplant TB, implying in a donor-derived origin. CONCLUSION: TB is an important differential diagnosis for infectious complications in patients after solid-organ transplantation, especially in endemic regions. Its initial clinical presentation can be unspecific and it should be suspected in the presence of fever or formation of fluid collections. The suspicion of TB is the key to early diagnosis and satisfactory outcomes in post-transplant TB.

Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction.

The rapid spread of multi-drug resistant pathogens represents a serious threat to public health, considering factors such as high mortality rates, treatment restrictions and high prevalence of multi-drug resistant bacteria in the hospital environment. Antimicrobial peptides (AMPs) may exhibit powerful antimicrobial activity against different and diverse microorganisms, also presenting the advantage of absence or low toxicity towards animal cells. In this study, the evaluation of the antimicrobial activity against multi-drug resistant bacteria of a recently described AMP from wasp, Polydim-I, was performed. Polydim-I presented activity against standard strains (non-carriers of multi-resistant genes) that are susceptible to commercial antimicrobials, and also against multi-drug resistant strains at concentrations bellow 1µg/ml (0.41 µM). This is a rather low concentration among those reported for AMPs. At this concentration we found out that Polydim-I inhibits almost 100% of the tested pathogens growth, while with the ATCC strains the minimum inhibitory concentration (MIC100) is 400 times higher. Also, in relation to in vitro activity of conventional drugs against multi-drug resistant bacteria strains, Polydim-I is almost 10 times more efficient and with broader spectrum. Cationic AMPs are known as multi-target compounds and specially for targeting the phospholipid matrix of bacterial membranes. Exploring the interactions of Polydim-I with lipid bilayers, we have confirmed that this interaction is involved in the mechanism of action. Circular dichroism experiments showed that Polydim-I undergoes a conformational transition from random coil to a mostly helical conformation in the presence of membrane mimetic environments. Zeta potential measurements confirmed the binding and partial charge neutralization of anionic asolectin vesicles, and also suggested a possible aggregation of peptide molecules. FTIR experiments confirmed that some peptide aggregation occurs, which is minimized in the presence of strongly anionic micelles of sodium dodecyl sulfate. Also, Polydim-I induced channel-like structures formation to asolectin lipid bilayers, as demonstrated in the electrophysiology experiments. We suggest that cationic Polydim-I targets the membrane lipids due to electrostatic attraction, partially accumulates, neutralizing the opposite charges and induces pore formation. Similar mechanism of action has already been suggested for other peptides from wasp venoms, especially mastoparans.

Polydim-I antimicrobial activity against MDR bacteria and its model membrane interaction

The rapid spread of multi-drug resistant pathogens represents a serious threat to public health, considering factors such as high mortality rates, treatment restrictions and high prevalence of multi-drug resistant bacteria in the hospital environment. Antimicrobial peptides (AMPs) may exhibit powerful antimicrobial activity against different and diverse microorganisms, also presenting the advantage of absence or low toxicity towards animal cells. In this study, the evaluation of the antimicrobial activity against multi-drug resistant bacteria of a recently described AMP from wasp, Polydim-I, was performed. Polydim-I presented activity against standard strains (non-carriers of multi-resistant genes) that are susceptible to commercial antimicrobials, and also against multi-drug resistant strains at concentrations bellow 1 mu g/ml (0.41 mu M). This is a rather low concentration among those reported for AMPs. At this concentration we found out that Polydim-I inhibits almost 100% of the tested pathogens growth, while with the ATCC strains the minimum inhibitory concentration (MIC100) is 400 times higher. Also, in relation to in vitro activity of conventional drugs against multi-drug resistant bacteria strains, Polydim-I is almost 10 times more efficient and with broader spectrum. Cationic AMPs are known as multi-target compounds and specially for targeting the phospholipid matrix of bacterial membranes. Exploring the interactions of Polydim-I with lipid bilayers, we have confirmed that this interaction is involved in the mechanism of action. Circular dichroism experiments showed that Polydim-I undergoes a conformational transition from random coil to a mostly helical conformation in the presence of membrane mimetic environments. Zeta potential measurements confirmed the binding and partial charge neutralization of anionic asolectin vesicles, and also suggested a possible aggregation of peptide molecules. FTIR experiments confirmed that some peptide aggregation occurs, which is minimized in the presence of strongly anionic micelles of sodium dodecyl sulfate. Also, Polydim-I induced channel-like structures formation to asolectin lipid bilayers, as demonstrated in the electrophysiology experiments. We suggest that cationic Polydim-I targets the membrane lipids due to electrostatic attraction, partially accumulates, neutralizing the opposite charges and induces pore formation. Similar mechanism of action has already been suggested for other peptides from wasp venoms, especially mastoparans.