Fosfomycin in severe infections due to genetically distinct pan-drug-resistant Gram-negative microorganisms: synergy with meropenem.

Background: In vitro and clinical studies using parenteral fosfomycin have suggested the possibility of using this drug against infections caused by MDR microorganisms. The aim of this study was to describe a case series of patients treated with fosfomycin who had severe infections caused by pan-drug-resistant Gram-negative bacteria. Methods: We describe a prospective series of cases of hospitalized patients with infections caused by Gram-negative bacteria resistant to ß-lactams and colistin, treated with 16 g of fosfomycin daily for 10-14 days. Isolates were tested for antimicrobial susceptibility and synergism of fosfomycin with meropenem. We tested for resistance genes and performed typing using PCR and WGS. Results: Thirteen patients received fosfomycin (seven immunosuppressed); they had bloodstream infections (n = 11; 85%), ventilator-associated pneumonia (n = 1; 8%) and surgical site infection (n = 1; 8%), caused by Klebsiella pneumoniae (n = 9), Serratia marcescens (n = 3) and Pseudomonas aeruginosa (n = 1). Overall, eight (62%) patients were cured. Using time-kill assays, synergism between fosfomycin and meropenem occurred in 9 (82%) of 11 isolates. Typing demonstrated that K. pneumoniae were polyclonal. Eight patients (62%) had possible adverse events, but therapy was not discontinued. Conclusions: Fosfomycin may be safe and effective against infections caused by pan-drug-resistant Gram-negative microorganisms with different antimicrobial resistance mechanisms and there seems to be synergism with meropenem.

Maternal infection by Leishmania braziliensis in hamster does not influence the course of disease in progeny / A infecção materna por Leishmania braziliensis em hamster não influencia o curso da doença na prole

Introduction: Immunoglobulins, soluble antigens, cells, cytokines and other immune system products can be transferred from infected mother to her offspring, leading to suppression or stimulation of immune response. Objective: To evaluate the influence of gender and maternal infection with Leishmania braziliensis in the course of the disease in the offspring of hamsters. Methods: Offspring born from infected mother (IMO) or non-infected mother (NIMO) by Leishmania braziliensis, both sexes, was infected with the same strain of the mother after 30 days of life and followed for 18 weeks. We evaluated the thickness of the lesion, parasite load and histology of the lesions. Results: The number of parasite in both lesions and lymph node of IMO offspring showed a significant reduction in the 5th week post-infection compared to the NIMO offspring; however, this did not correspond to clinical symptoms. Histopathological analysis revealed that in the IMO offspring, the inflammatory process was more prominent. In relation to gender, it was observed that the male offspring showed lesion thickness and higher parasite burden than females. Conclusion: Maternal infection by L. braziliensis in hamsters does not appear to influence the course of the disease in the homologous offspring infection, as well as the male offspring presented augmented susceptibility to L. braziliensis infection regardless of whether they were born from IMO or NIMO. Also, the reduction of the granuloma index in the IMO offspring, together with the higher inflammatory response, suggests a less effective cellular response in the chronic phase of the disease in these animals. (AU)

Introdução: Imunoglobulinas, antígenos solúveis, células, citocinas e outros produtos do sistema imune podem ser transferidos de mãe infectada para a sua prole, levando à supressão ou estimulação da resposta imune. Objetivo: Avaliar a influência do gênero e a infecção materna por Leishmania braziliensis no curso da doença na prole de hamsters. Métodos: Filhotes nascidos de mãe infectada (MI) e mãe não infectada (MNI) por L. braziliensis, ambos os sexos, foram infectados com a mesma cepa da mãe após 30 dias de vida e acompanhados por 18 semanas. Avaliou-se a espessura da lesão, a carga parasitária e os aspectos histopatológicos das lesões. Resultados: A carga parasitária (lesões e linfonodo de drenagem das lesões) da prole nascida de MI mostrou diminuição significativa na 5a semana pós-infecção, comparada àquela nascida de MNI, no entanto, esta diminuição não correspondeu aos sintomas clínicos. A análise histopatológica revelou que na prole nascida de MI, o processo inflamatório mostrou-se mais proeminente. Em relação ao gênero observou-se que os filhotes machos apresentaram espessura das lesões e carga parasitária maiores do que as fêmeas. Conclusão: A infecção materna por L. braziliensis parece não influenciar o curso da doença na infecção homóloga da prole, bem como os filhotes machos apresentaram aumentada susceptibilidade à infecção por L. braziliensis, independente se eles nasceram de MI ou MNI. Além disso, a redução no index de granulomas na prole nascida de MI, em conjunto com a maior resposta inflamatória, sugere uma resposta celular menos efetiva na fase crônica da doença nestes animais. (AU)