Combinatory antibiotic therapy increases rate of bacterial kill but not final outcome in a novel mouse model of Staphylococcus aureus spinal implant infection

BACKGROUND:Management of spine implant infections (SII) are challenging. Explantation of infected spinal hardware can destabilize the spine, but retention can lead to cord compromise and biofilm formation, complicating management. While vancomycin monotherapy is commonly used, in vitro studies have shown reduced efficacy against biofilm compared to combination therapy with rifampin. Using an established in vivo mouse model of SII, we aim to evaluate whether combination therapy has increased efficacy compared to both vancomycin alone and infected controls. METHODS:An L-shaped, Kirschner-wire was transfixed into the L4 spinous process of 12-week-old C57BL/6 mice, and inoculated with bioluminescent Staphylococcus aureus. Mice were randomized into a vancomycin group, a combination group with vancomycin plus rifampin, or a control group receiving saline. Treatment began on post-operative day (POD) 7 and continued through POD 14. In vivo imaging was performed to monitor bioluminescence for 35 days. Colony-forming units (CFUs) were cultured on POD 35. RESULTS:Bioluminescence peaked around POD 7 for all groups. The combination group had a 10-fold decrease in signal by POD 10. The vancomycin and control groups reached similar levels on POD 17 and 21, respectively. On POD 25 the combination group dropped below baseline, but rebounded to the same level as the other groups, demonstrating a biofilm-associated infection by POD 35. Quantification of CFUs on POD 35 confirmed an ongoing infection in all three groups. CONCLUSIONS:Although both therapies were initially effective, they were not able to eliminate implant biofilm bacteria, resulting in a rebound infection after antibiotic cessation. This model shows, for the first time, why histologic-based, static assessments of antimicrobials can be misleading, and the importance of longitudinal tracking of infection. Future studies can use this model to test combinations of antibiotic therapies to see if they are more effective in eliminating biofilm prior to human trials

Síndrome pulmonar e cardiovascular por hantavírus Hantavirus pulmonary and cardiovascular syndrome

A síndrome pulmonar e cardiovascular por hantavírus é uma doença de conhecimento relativamente recente e freqüentemente fatal, apresentando-se como síndrome do desconforto respiratório agudo. No Brasil, desde o primeiro surto, relatado em novembro/dezembro de 1993, em Juquitiba, 226 casos já foram registrados pela Fundação Nacional da Saúde. A doença afeta indivíduos previamente hígidos, apresentando-se com pródromo febril e sintomas semelhantes aos de um resfriado comum, podendo rapidamente evoluir para edema pulmonar, insuficiência respiratória aguda e choque. A hemoconcentração e a plaquetopenia são comuns da síndrome pulmonar e cardiovascular por hantavírus, e o quadro radiológico típico é de um infiltrado intersticial bilateral difuso, que progride rapidamente para consolidações alveolares, paralelamente à piora do quadro clínico. A mortalidade inicial era em torno de 75% e declinou para aproximadamente 35%, nos últimos anos. Os pacientes que sobrevivem geralmente recuperam-se completamente, cerca de uma semana após o estabelecimento do quadro respiratório. O agente causal, não reconhecido até há pouco, foi identificado como um hantavírus, cujo reservatório natural são animais roedores da família Muridae, subfamília Sigmodontinae. O tratamento específico antiviral ainda não é bem estabelecido, estando em estudo a eficácia de ribavirina. Cuidados de terapia intensiva como ventilação mecânica e monitoramento hemodinâmico invasivo são necessários nas formas mais graves da doença. Essas medidas, se instituídas precocemente, podem melhorar o prognóstico e a sobrevida dos pacientes com síndrome pulmonar e cardiovascular por hantavírus.<br>Hantavirus pulmonary and cardiovascular syndrome is a recently identified and often fatal disease, which presents as acute respiratory distress syndrome (ARDS). Since the first outbreak, in Nov/Dec 1993, in Juquitiba, Brazil, 226 cases have been registered by FUNASA (National Health Foundation).(4) The disease occurs in previously healthy subjects, presenting with fever and symptoms similar to the common cold, and may rapidly evolve to pulmonary edema, respiratory failure and shock. Hemoconcentration and thrombocytopenia are common features, and the typical radiological finding is a bilateral diffuse interstitial infiltrate that evolves to alveolar consolidations in parallel to the worsening of the clinical condition. Initially, mortality was around 75%, but it declined to approximately 35% in the last few years. Patients who survive usually recover completely, about a week after the onset of the respiratory symptoms. The causal agent is a previously unrecognized hantavirus whose natural reservoirs are rodents of the family Muridae, sub-family Sigmodontinae. Specific antiviral treatment for hantavirus pulmonary and cardiovascular syndrome has not yet been well established, and the efficacy of ribavirin is currently being studied. Intensive care, including mechanical ventilation and invasive hemodynamic monitoring, is required for the more severe presentations of the disease. These measures may improve the prognosis and survival of patients with hantavirus pulmonary and cardiovascular syndrome if started early in the course of the disease